curcumin and Hemolysis

Cyclodextrins (CDs) are natural cyclic oligosaccharides with a relatively hydrophobic cavity and a hydrophilic outer surface. In this study, alpha (α-), beta (β-) and gamma (γ-) CD particles were prepared by directly using α-, β-, and γ-CDs as monomeric units and divinyl sulfone (DVS) as a crosslinker in a single-step via reverse micelle microemulsion crosslinking technique. Particles of p(α-CD), p(β-CD), and p(γ-CD) were perfectly spherical in sub- 10 µm size ranges. The prepared p(CD) particles at 1.0 mg/mL concentrations were found biocompatible with > 95 % cell viability against L929 fibroblasts. Furthermore, p(α-CD) and p(β-CD) particles were found non-hemolytic with < 2 % hemolysis ratios, whereas p(γ-CD) particles were found to be slightly hemolytic with its 2.1 ± 0.4 % hemolysis ratio at 1.0 mg/mL concentration. Furthermore, a toxic compound, Bisphenol A (BPA) and a highly antioxidant polyphenol, curcumin (CUR) complexation with α-, β-, and γ-CD molecules was investigated via Electrospray-Ion Mobility-Mass Spectrometry (ESI-IM-MS) and tandem mass spectrometry (MS/MS) analysis. It was determined that the most stable noncovalent complex was in the case of β-CD, but the complex stoichiometry was changed by the hydrophobic nature of the guest molecules. In addition, BPA and CUR were separately loaded into prepared p(CD) particles as active agents. The drug loading and release studies showed that p(CD) particles possess governable loading and releasing profiles.

Topics: Biological Availability; Curcumin; Cyclodextrins; Drug Delivery Systems; Hemolysis; Humans; Tandem Mass Spectrometry

In this study, carboxylated carbon nanotube (CNT)-loaded curcumin (CUR) was blended into calcium phosphate cement (CPC) owing to the poor mechanical properties and single function of CPC as a bone-filling material, and CNT-CUR-CPC with improved strength and antitumor properties was obtained. The failure strength, hydrophilicity, in vitro bioactivity, bacteriostatic activity, antitumor activity, and cell safety of CNT-CUR-CPC were evaluated. The experimental results indicated that the failure strength of CNT-CUR-CPC increased from 25.05 to 45.05 MPa (

Topics: Bone Cements; Calcium Phosphates; Compressive Strength; Curcumin; Durapatite; Hemolysis; Humans; Materials Testing; Nanotubes, Carbon

Healing of various skin wounds is a lengthy process and often combined with bacterial infection and scar formation. Biomimetic electrospun nanofibrous wound dressing loaded with materials that possess properties of dual antibacterial and tissue repair would be developed to address this problem. In this study, a composite chitosan electrospun nanofibrous material containing Cur@β-CD/AgNPs nanoparticles composed of silver and curcumin possessed synergic effects on antibacterial activity and wound healing. The developed functionalized silver nanoparticles showed effective activity against both Gram-negative and Gram-positive bacteria. In vivo, Cur@β-CD/AgNPs chitosan dressing displayed enhanced wound closure rates compared to commercial AquacelAg. Moreover, Cur@β-CD/AgNPs chitosan dressing contributed to the most uniform collagen distribution by Masson's trichrome staining. In brief, Cur@β-CD/AgNPs chitosan nanofibers work as a potential wound dressing with antibacterial and antiscarring properties.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bandages; Cells, Cultured; Chitosan; Curcumin; Electrochemical Techniques; Erythrocytes; Hemolysis; Male; Metal Nanoparticles; Mice; Nanofibers; Silver; Skin; Wound Healing

Pullulanase debranching and subsequent hydroxypropylation were applied to prepare a series of dual-modified starches (Hydroxypropylated debranched starch, HPDS) with different degrees of hydroxypropyl substitution. Their structural and physicochemical properties varied with the degree of hydroxypropyl substitution, and all HPDS exhibited the ability to self-assemble into well-shaped nanospheres (100-150 nm, PDI < 0.2). These HPDS nanospheres were attempted to encapsulate curcumin with the aim of improving the bioavailability, solubility and stability of curcumin. Their structural characteristics, thermal stability, iodine staining, morphology, safety, encapsulation efficiency, in vitro gastrointestinal release behavior, and anti-inflammatory activity were evaluated. The results showed that curcumin could be effectively encapsulated into the HPDS nanospheres, and the encapsulation efficiency, water solubility and physical stability were positively correlated with the degree of hydroxypropyl substitution. After encapsulation, the water solubility and physical stability of curcumin could be increased up to 226-fold and 6-fold, respectively. The HPDS nanospheres also exhibited good safety (including hemolysis and cytotoxicity) and sustainable release of curcumin. Evaluation of anti-inflammatory activity showed that the activity of curcumin-encapsulated HPDS was enhanced by 170% compared to unencapsulated curcumin. These suggest that HPDS nanospheres encapsulation may be a more suitable option for the development of functional foods containing bioactive compounds.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Caco-2 Cells; Cell Survival; Curcumin; Drug Liberation; Hemolysis; Humans; Nanospheres; Solubility; Starch

An oxovanadium(IV) - curcumin based complex, viz. [VO(cur)(2,2´-bipy)(H

Topics: Animals; Binding Sites; Cattle; Coordination Complexes; Curcumin; DNA; DNA Gyrase; Escherichia coli; Escherichia coli Proteins; Hemolysis; Humans; Ligands; Molecular Docking Simulation; Protein Binding; Serum Albumin, Bovine; Vanadium; Viscosity

Due to its high therapeutic efficiency and low systemic toxicity, natural bioactive curcumin has attracted more and more attention as a potential antineoplastic drug. Although the emergence of a carrier-free nanocrystalline technology could improve the solubility and guarantee the high drug loading of curcumin, uncontrollable drug release and fast systemic metabolism are definite obstacles that hinder its further application in cancer treatment. Here, hyaluronic acid (HA) modification was carried out on the surface of curcumin nanocrystals (Cur-NC) to obtain surface reformed hydrophilic HA@Cur-NCs that exhibit prolonged biodistribution. Besides this, HA@Cur-NC shows enhanced intracellular uptake in CD44 overexpressing MDA-MB-231 cells, but reduced uptake when pre-treated with HA. The apoptotic effects, confirmed by flow cytometry, suggest that HA@Cur-NC could achieve high anticancer activity against MDA-MB-231 cells. In vivo pharmacokinetic studies suggest that the t

Topics: Animals; Breast Neoplasms; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Survival; Curcumin; Drug Carriers; Drug Liberation; Female; Half-Life; Hemolysis; Humans; Hyaluronic Acid; Hydrophobic and Hydrophilic Interactions; Mice; Mice, Inbred BALB C; Nanoparticles; Rats; Rats, Sprague-Dawley; Tissue Distribution

Chemotherapeutic agents with different anticancer mechanisms could enhance therapeutic effect in cancer therapy by their combined application. In this study, redox-sensitive prodrug nanoparticles based on Xyl-SS-Cur conjugate were developed for co-delivery of curcumin and 5-FU in cancer therapy. The Xyl-SS-Cur conjugate was synthesized via covalent conjugation of curcumin to xylan through a disulphide (-S-S-) linkage. The Xyl-SS-Cur conjugate could self-assemble in aqueous medium into nanoparticles and the lipophilic 5-fluorouracil-stearic acid (5-FUSA) prodrug was encapsulated into the hydrophobic core of Xyl-SS-Cur NPs through dialysis membrane method. The obtained Xyl-SS-Cur/5-FUSA NPs had an appropriate size (∼217 ± 2.52 nm), high drug loading of curcumin (∼ 31.4 wt%) and 5-FUSA (∼ 11.8 wt%) and high stability. The interaction of Xyl-SS-Cur/5-FUSA NPs with blood components was investigated by hemolysis study. The cytotoxicity study demonstrated that Xyl-SS-Cur/5-FUSA NPs induced higher cytotoxicity than free drugs against the Human colorectal cancer cells (HT-29, HCT-15). These results indicate that Xyl-SS-Cur/5-FUSA NPs can serve as a promising drug delivery system in cancer therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Curcumin; Disulfides; Drug Delivery Systems; Drug Liberation; Drug Stability; Fluorouracil; Hemolysis; HT29 Cells; Humans; Nanoparticles; Neoplasms; Oxidation-Reduction; Particle Size; Prodrugs; Spectroscopy, Fourier Transform Infrared; Stearic Acids; Xylans

Glutaraldehyde (GA) crosslinked bovine or porcine pericardium tissues exhibit high cell toxicity and calcification in the construction of bioprosthetic valves, which accelerate the failure of valve leaflets and motivate the exploration for alternatives. Polyphenols, including curcumin, procyanidin and quercetin, etc, have showed great calcification inhibition potential in crosslinking collagen and elastin scaffolds. Herein, we developed an innovative phenolic fixing technique by using curcumin as the crosslinking reagent for valvular materials. X-ray photoelectron spectroscopy and Fourier transform infrared spectrometry assessments confirmed the hydrogen bond between curcumin and acellular bovine pericardium. Importantly, the calcification inhibition capability of the curcumin-crosslinked bovine pericardium was proved by the dramatically reduced Ca

Topics: Animals; Bioprosthesis; Calcification, Physiologic; Cattle; Collagen; Cross-Linking Reagents; Curcumin; Elastin; Glutaral; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valves; Hemolysis; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Bonding; In Vitro Techniques; Materials Testing; Osteogenesis; Pericardium; Phenol; Photoelectron Spectroscopy; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Stress, Mechanical; Thermodynamics

Using Chitosan/PEO as the shell and PCL as the core, chitosan-polyethylene oxide/polycaprolactone nanofibrous mats were prepared successfully by coaxial electrospinning for co-load and sequential co-delivery of two drugs. Herein, lidocaine hydrochloride (Lid), used for pain relief, was added to the shell, and curcumin (Cur), an anti-inflammatory agent, was introduced into the core. Sodium bicarbonate (SB) was also added to the core layer to provide wound microenvironment sensitivity. Under acidic conditions, Lid was released due to the formation of -NH3+ by protonation of -NH2 on the chitosan molecular chains. At the same time, SB reacted with hydrogen ions to generate CO2, and many holes were generated on the surface of the fibers, providing more discharge paths for Cur release. Additionally, both Lid in the shell layer and Cur in the core layer exhibited acidic pH (∼5.4)-responsive release profiles. Moreover, a rapid release of Lid and a sustained release of Cur were observed to provide the immediate effects of analgesia and long-term antibacterial activity in the process of wound healing. Furthermore, after 48 h incubation, the mats showed continuous and excellent antibacterial performance against E. coli and S. aureus. The results of blood coagulation showed that the mats could achieve rapid hemostasis in the early stage of wound formation. Hemolytic and cytotoxicity evaluation also revealed that the mats had excellent hemocompatibility and cytocompatibility. Therefore, this study has made invaluable contributions to the design of a dual-drug-loaded dressing with microenvironment-responsive and sequential release properties towards wound care.

Topics: Animals; Anti-Bacterial Agents; Biocompatible Materials; Cell Line; Cell Survival; Chitosan; Curcumin; Drug Carriers; Drug Liberation; Escherichia coli; Hemolysis; Hydrogen-Ion Concentration; Mice; Nanofibers; Polyesters; Polyethylene Glycols; Rabbits; Sodium Bicarbonate; Staphylococcus aureus; Wound Healing

In this research, curcumin (CUR) conjugated albumin based nanoparticles (BSA-CUR) were designed for improvement and evaluation radioprotective effect of CUR. In this way, we have prepared BSA-CUR by covalently binding the CUR with BSA. Next, this synthesized prodrug was evaluated for physical and chemical properties by Fourier-transform infrared (FTIR), Dynamic light scattering (DLS), Transmission electron microscopy (TEM), Ultraviolet-visible (UV/Vis), and Differential scanning calorimetry (DSC) analysis. Furthermore, the chemical stability of designed prodrug was appraised. The result shows that the size of nanoparticles is 174.4 nm with a polydispersity index (PdI) of 0.191. The nanoparticles have a high loading capacity and show sustained release behavior. Loading of CUR to BSA not only could increase the chemical stability of CUR, but also could improve radioprotection efficacy of it's against X-Ray irradiation. The HHF-2 cells show 107% viability in the presence of BSA-CUR at a concentration of 50 µg/mL, whereas non-treated cells show 46% viability, under X-Ray irradiation. Also in vivo study results show that, four out of five mice have died when the mice irradiated by X-Ray and no received any treatment. Although, for a group that treated with BSA-CUR and also irradiated by X-Ray, median survival and survival rate was higher than CUR treated and control mice, and only two out of five mice have died. The result of this study proved that BSA-CUR can be used as a proficient vehicle for improving the potential radioprotective effect of CUR.

Topics: Animals; Cattle; Cell Line; Cell Survival; Curcumin; Drug Carriers; Hemolysis; Humans; Mice, Inbred BALB C; Nanoparticles; Prodrugs; Radiation-Protective Agents; Serum Albumin, Bovine; X-Rays

The ever increasing demand for nanoantioxidants with minimized toxicity dictates the necessity to develop new biocompatible materials. One promising approach is the immobilization of polyphenols on metal (oxy)hydroxide nanoparticles (NPs) that possess the desired chemical and colloidal stability while also allowing to dispose of the antioxidants more safely and effectively. In this paper we modify sol-gel synthesized γ-AlOOH NPs with curcumin molecules. The prepared colloidal systems are hydrosols, stable in acidic, neutral and slightly basic pH values. UV-vis and FTIR spectroscopies suggest that the mechanism of curcumin binding lies in the H-bonding of its functional groups to hydroxyls of pseudoboemite. Modification of AlOOH nanoparticles shifts its isoelectric point from 9.7 to 9.3 due to the weak acidic centers of the polyphenol. Immobilization of curcumin molecules on pseudoboehmite allows to achieve good solubility of the phenol in water and to reduce the level of its hemolytic activity (indicating good biocompatibility). At the same time, it preserves radical scavenging activity and in some experimental designs even enhances antioxidant and membrane-protective activity (enhancement ≥30%) in vitro on cellular and non-cellular models.

Topics: Aluminum Hydroxide; Aluminum Oxide; Animals; Antioxidants; Curcumin; Drug Carriers; Erythrocyte Membrane; Hemolysis; Metal Nanoparticles; Mice; Oxidative Stress

To develop docetaxel (DT) and curcumin (CUR) co-loaded nanostructured lipid carriers (DTCR-NLCs) for ratiometric co-targeting to non-small cell lung carcinoma (NSCLC) cells.. The DTCR-NLCs were developed by employing a high-pressure homogenisation technique and optimised by employing a rotatable central composite design response surface methodology (RCCD-RSM) via the design of experiments (DoE) approach.. The optimised DTCR-NLCs had a particle size (D90) of 150.2 ± 5.2 nm, Pdi of 0.263 ± 0.15, zeta potential of +26.3 ± 5.2 mv. The % drug loading (% DL) of DT and CUR was observed to be 1.38 ± 0.98 and 2.99 ± 1.24, respectively. Dissolution studies depicted a pH-independent drug release (≈98% drug release at 144 h). The DTCR-NLCs were stable and haemocompatible. MTT cell viability assay of DTCR-NLCs demonstrated considerably increased cytotoxicity towards NCI-H460 cells.. The developed DTCR-NLCs heralds the future of an efficacious and safer Taxane therapy for NSCLC.

Topics: Antineoplastic Agents; Calorimetry, Differential Scanning; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Survival; Cobalt; Curcumin; Docetaxel; Drug Delivery Systems; Drug Screening Assays, Antitumor; Hemolysis; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Lipids; Lung Neoplasms; Microspheres; Nanostructures; Particle Size; Temperature; Tetrazolium Salts; Thiazoles; X-Ray Diffraction

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Chromatography; Curcuma; Diarylheptanoids; Dose-Response Relationship, Drug; Flow Cytometry; Gene Expression; Hemolysis; Humans; Leukemia; Leukocytes, Mononuclear; Mice; Molecular Structure; Plant Extracts; RAW 264.7 Cells; Rhizome; WT1 Proteins

Colorectal cancer (CRC) is a prevalent and fatal cancer. Oral administration provided the potential for in situ treatment of the colorectal cancer. However, drugs couldn't be well-absorbed mainly due to its degradation in the gastric area and poor intestinal permeability. In this study, we synthesized deoxycholic acid and hydroxybutyl decorated chitosan nanoparticles (DAHBC NPs) as oral curcumin (CUR) delivery system for colorectal cancer treatment. DAHBC with lower critical solution temperature (LCST) below 37 °C (27-33 °C) was obtained. DAHBC NPs were correspondingly stable in simulated gastric conditions (pH 1.2, 37 °C), due to the offset of size change between pH-responsive expansion and thermo-responsive shrinkage. In simulated intestinal tract (pH 7.0-7.4, 37 °C), DAHBC NPs exhibited burst release of CUR owing to the onefold effect of thermo-responsive shrinkage. DAHBC27 NPs showed the minimum CUR leakage (~10%) in simulated gastric conditions, because a furthest temperature-sensitive shrinkage caused by the lowest LCST offset the expansion in acid environment. DAHBC27 NPs induced ~10-fold increased (P < 0.05) CUR absorption by paracellular transport pathway, compared to the free CUR. Thus, DAHBC NPs stabilized in the gastric environment may be a promising oral drugs delivery system for effective in situ colorectal cancer therapy.

Topics: Administration, Oral; Adsorption; Caco-2 Cells; Chitosan; Colorectal Neoplasms; Curcumin; Deoxycholic Acid; Drug Carriers; Drug Liberation; Drug Stability; Gastric Mucosa; Hemolysis; Humans; Intestinal Absorption; Materials Testing; Nanoparticles; Temperature

The problems associated with hydrophobic anticancer drugs are among the most important challenges to achieve efficient therapeutics for cancer treatment. In this study, PEGylated curcumin was used as the surface modification of magnetic nanoparticles (MNP@PEG-Cur) in order to simultaneously take advantage of magnetic targeting characteristic of nanoparticles and PEG conjugated drug. Curcumin was conjugated through EDC/NHS chemistry to the PEG hydroxyl functional groups, and then physically decorated on the surface of magnetic nanoparticles (MNP). The analysis of the conjugate and nanoparticles by FT-IR,

Topics: Animals; Biocompatible Materials; Cell Survival; Curcumin; Drug Delivery Systems; Drug Liberation; Hemolysis; Humans; Magnetic Fields; Magnetite Nanoparticles; MCF-7 Cells; Mice; Polyethylene Glycols; Proton Magnetic Resonance Spectroscopy; Spectroscopy, Fourier Transform Infrared; Thermogravimetry

Curcumin, the main bioactive polyphenolic compound in Curcuma longa L. rhizomes has a wide range of bioactive properties. Curcumin presents low solubility in water and thus limited bioavailability, which decreases its applicability. In this study, cytotoxic effects of curcumin solid dispersions (CurSD) were evaluated against tumor (breast adenocarcinoma and lung, cervical and hepatocellular carcinoma) and non-tumor (PLP2) cells, while cytotoxic and genotoxic effects were evaluated in Allium cepa. The effect of the CurSD on the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), glutathione S-transferase (GST), and monoamine oxidase (MAO A-B) enzymes was determined, as well as its capacity to inhibit the oxidative hemolysis (OxHLIA) and the formation of thiobarbituric acid reactive substances (TBARS). CurSD are constituted by nanoparticles that are readily dispersible in water, and inhibited 24% and 64% of the AChE and BChE activity at 100 μM, respectively. GST activity was inhibited at 30 μM while MAO-A and B activity were inhibited at 100 μM. CurSD showed cytotoxicity against all the tested tumor cell lines without toxic effects for non-tumor cells. No cytotoxic and genotoxic potential was detected with the Allium cepa test. CurSD maintained the characteristics of free curcumin on the in vitro modulation of important enzymes without appreciable toxicity.

Topics: Animals; Antioxidants; Carcinogens; Cell Line, Tumor; Curcumin; Dosage Forms; Enzyme Inhibitors; Hemolysis; Humans; Mice; Mutagens; Nitric Oxide; Onions; Oxidation-Reduction; Rats; RAW 264.7 Cells; Thiobarbituric Acid Reactive Substances

Graphene-based nanomaterials (GBNMs) have great potential in drug delivery and photothermal therapy owing to their unique physicochemical properties. However, inferior water solubility and biocompatibility related issues greatly restricted their further applications. Herein, to rectify the obstructive problems, we prepared uniform and smaller sized graphene oxide (GO) nanosheets (∼85 nm) via a modified Hummers' method, which exhibited significantly improved hemocompatibility compared to random large sized GO nanosheets prepared by a common method. Then, we grafted unfractionated heparin (UFH) onto reduced graphene oxide (rGO) covalently using adipic acid dihydrazide (ADH) as a linker to fabricate biocompatible nanocomposites for the cellular delivery of curcumin (Cur). The novel nanocomposites showed quite a small size of 42 nm in average lateral dimension and exhibited a significantly stronger photothermal effect than GO nanosheets. Besides, in vitro cell experiments verified that the potential anticancer efficacy of Cur-loaded vehicles and cytotoxicity of rGO-UFH/Cur against MCF-7 and A549 cells could be further enhanced under 808 nm irradiation, suggesting the possibility of combinational chemotherapy and photothermal therapy. Moreover, consistent with the in vitro sustained drug release performance, an in vivo pharmacokinetics study also indicated that the retention time of Cur could be significantly prolonged when loaded on rGO-UFH nanocomposites than in free Cur solution. Notably, we firstly discussed the interaction between rGO and Cur, and demonstrated the meliorative biocompatibility of uniform rGO compared to GRO via a molecular dynamics simulation (MD) study. Thus, the in vitro, in vivo and computational study demonstrated that the small sized rGO-UFH nanocomposites had wide application prospects as drug delivery vehicles.

Topics: A549 Cells; Animals; Apoptosis; Biocompatible Materials; Curcumin; Drug Liberation; Graphite; Half-Life; Hemolysis; Heparin; Humans; Infrared Rays; Male; MCF-7 Cells; Molecular Dynamics Simulation; Nanocomposites; Proteins; Rats; Rats, Wistar; Tissue Distribution

This paper aims at demonstrating silk fibroin nanoparticles (SFNs) promote anti-inflammatory properties of celecoxib (CXB) or curcumin (CUR), and could be exploited for osteoarthritis (OA) treatment. Nanoparticles were prepared by desolvation method and physico-chemically characterized (FT-IR, DSC, TGA, SEM, size distribution and drug release); empty and drug loaded nanoparticles were tested for their ROS-scavenging activity, hemolytic properties, cytotoxicity, and anti-inflammatory potency in an OA in vitro model. Results indicate that a controlled drug release has been achieved by varying the drug loading. Curcumin plus SFNs exhibited a synergistic antioxidant effect, while CXB was, in some manner, inhibitory. Both free drugs resulted highly cytotoxic while cell viability reached high values when encapsulated in SFNs. No appreciable differences in anti-inflammatory activity was evidenced between CUR loaded SFNs and CXB. In conclusion, SFNs is an optimal carrier to improve cyto- and hemo-compatibility of both CUR and CXB.

Topics: Anti-Inflammatory Agents; Antioxidants; Celecoxib; Cell Survival; Cells, Cultured; Curcumin; Drug Delivery Systems; Drug Liberation; Drug Synergism; Fibroins; Hemolysis; Humans; Nanoparticles; Osteoarthritis; Particle Size; Reactive Oxygen Species

In this work, a multifunctional magnetic Bio-Metal-Organic Framework (Fe

Topics: Animals; Biocompatible Materials; Cell Death; Cell Line, Tumor; Cell Survival; Chitosan; Curcumin; Drug Liberation; Erythrocytes; Ferric Compounds; Fluorouracil; Folic Acid; Hemolysis; Humans; Magnetic Resonance Imaging; Magnetics; Metal-Organic Frameworks; Mice; Mice, Inbred BALB C; Nanocomposites; Neoplasms; NIH 3T3 Cells; Phantoms, Imaging; Protein Corona; Theranostic Nanomedicine; X-Ray Diffraction

Targeted liposomes with different combinations of five ligands (for brain/amyloid targeting) were evaluated for hemocompatibility. Results reveal that all liposomes studied, caused minimum hemolysis; targeted liposomes slightly reduced blood coagulation time, but not significantly more than control liposomes; and compliment factors SC5b9 and iC3b increased when compared with the buffer, by most targeted liposomes. However, the specific amounts of both factors were similar with those induced by control liposomes. Thus, the targeted liposomes are unanticipated to cause hypersensitivity problems. Good correlations between vesicle size and produced factor amounts were observed. In conclusion, the current targeted liposomes are not expected to cause serious blood toxicity, if used

Topics: Amyloid; Antibodies, Monoclonal; Apolipoproteins E; Biocompatible Materials; Blood Coagulation; Brain; Complement C3b; Complement Membrane Attack Complex; Curcumin; Ethanolamines; Hemolysis; Humans; Liposomes; Nanoparticles; Particle Size; Phosphatidylcholines

Dual stimuli responsive polyelectrolyte nanoparticles have been developed for chemo-photothermal synergistic therapy of colon cancer cells. This novel system is formed by layer by layer (LbL) assembly, which is composed of aminated nanodextran (AND) and carboxylated nanocellulose (CNC) deposited on the surface of chemically modified graphene oxide (MGO). The alternate layers of cationic AND and anionic CNC interact with MGO through electrostatic interaction and forms MGO-AND/CNC nanocomposite. The MGO-AND/CNC exploited for the encapsulation of anticancer drug curcumin (CUR) by π-π stacking and hydrogen bonding interactions. Various concentrations of MGO and AND/CNC were examined and the optimal hydrodynamic size of the particle was found to have 158.0 nm, zeta potential of -45.9 ± 6.9 mV and encapsulation efficiency of 86.4 ± 4.7%. The resulting nanocomposite was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering and zeta potential measurements. Drug release assay indicates that the LbL MGO-AND/CNC releases much faster in an acidic environment than intestinal pH. A cytotoxicity assay was conducted to prove the efficacy of drug loaded MGO-AND/CNC to destroy HCT116 cells in response to near-infrared (NIR) laser emission. Study results suggest the novel dual-sensitive nanoparticles allow intracellular curcumin delivery and respond to either acidic environments or NIR excitation.

Topics: Antineoplastic Agents; Cellulose; Combined Modality Therapy; Curcumin; Dextrans; Drug Carriers; Drug Liberation; HCT116 Cells; Hemolysis; Humans; Hydrogen Bonding; Hydrogen-Ion Concentration; Materials Testing; Nanoparticles; Phototherapy; Polyelectrolytes

The present investigation was undertaken to evaluate the antibacterial, antifungal and hemolytic activities of organic and aqueous fractions of Fumaria indica, Dicliptera bupleuroides and Curcuma zedoaria. The methanolic extracts of the plants were dissolved in the water (distilled) separately and then partitioned with the n-hexane, CHCl3, EtOAc and n-BuOH sequentially. Antibacterial activity was checked against Escherichia coli, Pasturella multocida, Bacillus subtilis and Staphylococcus aureus by the disc diffusion method using streptomycin sulphate, a standard antibiotic, as positive control. Antifungal activity was studied against four fungi i.e. Aspergillus niger, Aspergillus flavus, Ganoderma lucidum and Alternaria alternata by the disc diffusion method using fluconazole, a standard antifungal drug, as positive control. It was revealed that aqueous fraction of F. indica showed very good antibacterial activity against P. multocida with zone of inhibition 26mm and MIC of 98μg/mL. Its CHCl3 and n-BuOH fractions also displayed good results. Its CHCl3 fraction showed good antifungal activity against G. lucidum with zone of inhibition 24mm and MIC of 115μg/mL. Other polar fractions of F. indica showed good activity against somefungal strains. The CHCl3 and EtOAc fractions of D. bupleuroides displayed good antibacterial activity against some bacterial strains. Its EtOAc fraction showed good antifungal activity only against G. lucidum. The CHCl

Topics: Acanthaceae; Anti-Bacterial Agents; Antifungal Agents; Curcuma; Drug Evaluation, Preclinical; Fumaria; Gram-Negative Bacteria; Gram-Positive Bacteria; Hemolysis; Hemolytic Agents; Humans; Microbial Sensitivity Tests; Plant Extracts; Plants, Medicinal

This study was focused on developing a drug carrier system composed of a polymer containing hydroxyapatite (HAp) shell and a magnetic core of iron oxide nanoparticles. Doxorubicin and/or curcumin were loaded into the carrier via a simple diffusion deposition approach, with encapsulation efficiencies (EE) for curcumin and doxorubicin of 93.03 ± 0.3% and 97.37 ± 0.12% respectively. The co-loading of curcumin and doxorubicin led to a total EE of 76.02 ± 0.48%. Release studies were carried out at pH 7.4 and 5.3, and revealed a greater extent of release at pH 5.3, showing the formulations to have potential applications in tumor microenvironments. Cytotoxicity assays, fluorescence imaging and flow cytometry demonstrated that the formulations could effectively inhibit the growth of MCF-7 (breast) and HEpG2 (liver) cancer cells, being more potent than the free drug molecules both in terms of dose and duration of action. Additionally, hemolysis tests and cytotoxicity evaluations determined the drug-loaded carriers to be non-toxic towards non-cancerous cells. These formulations thus have great potential in the development of new cancer therapeutics.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Proliferation; Curcumin; Doxorubicin; Drug Carriers; Durapatite; Female; Ferric Compounds; Flow Cytometry; Hemolysis; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Liver Neoplasms; Male; MCF-7 Cells; Nanoparticles; Optical Imaging; Polymers; Rats, Wistar

Curcumin (CUR) is a natural diketone with diverse bioactivities of inhibiting angiogenesis and tumor growth. However, its clinical application for cancer treatment was severely hindered by poor aqueous solubility and chemical instability. To overcome these drawbacks and achieve enhanced antitumor efficiency, low molecular weight heparin (LMWH) was conjugated to CUR via the one-step esterification reaction to yield LMWH-CUR (LCU) nanodrugs with the size of 180 nm, which exhibited enhanced accumulation within tumor site by EPR effect and long circulating capacity by LMWH hydrophilic shell. The solubility of conjugated CUR was increased to 0.12 mg/mL (equivalent of CUR) in comparison with 0.006 mg/mL of free CUR. The bioactivities of CUR were guaranteed because of the improved stability of LCU nanodrugs in low pH condition. Moreover, the stronger anti-angiogenesis efficacy of LCU nanodrugs than LMWH monotherapy was also verified. Notably, at a rather low dose of equivalent LMWH (5 mg/kg) and CUR (0.3 mg/kg), the tumor inhibition rate of LCU nanodrugs were much higher than that of LMWH (10 times) and LMWH plus CUR mixture (3.8 times) respectively, indicating its excellent in vivo antitumor efficacy. Overall, our study managed to obtain the novel nanodrugs with potent anti-angiogenesis and antitumor effects whereas avoiding tedious and complicated synthetic procedures. These results also suggested that LCU nanodrugs could be considered as a promising targeted delivery system for cancer treatment.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Blood Coagulation; Cell Survival; Curcumin; Drug Combinations; Drug Stability; Erythrocytes; Hemolysis; Hep G2 Cells; Humans; Mice; Nanoparticles; Neoplasms; Rabbits; Tumor Burden

This study described a curcumin (CUR) loaded bovine serum albumin nanoparticles (BSA@CUR NPs), which could solubilize the poorly water-soluble drug and increase the therapeutic efficacy of the drug. BSA@CUR NPs were synthesized by a simple coacervation procedure. The resultant BSA@CUR NPs showed a spherical shape, with a diameter of 92.59±16.75nm (mean ± SD) nm and a ζ-potential of - 9.19mV. The in vitro drug release study of CUR showed a sustained and controlled release pattern. Cellular toxicity of BSA NPs was also investigated on HFF2 cell lines. Additionally, a hemolysis test of as prepared NPs were performed for investigation of hemocompatibility. Hemolysis assay and cytotoxicity study results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. The in vitro anticancer activity of the BSA@CUR NPs were performed by MTT assay on MCF-7 cancer cells. These results suggest that BSA@CUR NPs are a new drug delivery system for cancer therapy.

Topics: Animals; Cattle; Cell Line; Curcumin; Delayed-Action Preparations; Drug Carriers; Hemolysis; Materials Testing; Nanoparticles; Serum Albumin, Bovine

Liposomes (LPs), a delivery vehicle for stabilizing drugs, the characteristics of being easy to aggregate and fuse limit its application. Polymer coating is a promising way to tackle these issues. In this study, the potential of carboxymethyl chitosan (CMCS) and quaternary ammonium chitosan (TMC)-coated liposomes (CMCS/TMC-LPs) for improving the oral delivery capacity of curcumin (CUR) was explored. CMCS/TMC-LPs were prepared by electrostatic adsorption in a layer-by-layer manner. CMCS/TMC-LPs were spherical and had not obvious change in particle size and morphology after storage at 4 °C for 7 and 14 days. CMCS/TMC-LPs possessed favorable gastric acid tolerance (the cumulative drug release rate <10%) due to stable structure. The hemolysis test and Cell Counting Kit-8 (CCK8) assay appeared satisfactory biocompatibility of CMCS/TMC-LPs. The pharmacokinetics exhibited that oral absolute bioavailability of CUR loaded CMCS/TMC-LPs was about 38%, which was around 6 folds and 3 folds higher than CUR loaded LPs and CUR loaded TMC-LPs, respectively. The in vivo experiments showed that CMCS/TMC-LPs could prolong the retention time of CUR in systemic circulation and generate high level of CUR in liver, spleen and lung. Thus, CMCS/TMC-LPs may be a promising carrier for improving the efficacy and safety of orally administered drugs.

Topics: Administration, Oral; Adsorption; Animals; Biological Availability; Caco-2 Cells; Chitosan; Curcumin; Delayed-Action Preparations; Drug Compounding; Erythrocytes; Fibroblasts; Hemolysis; Humans; Liposomes; Liver; Lung; Male; Mice; Particle Size; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley; Spleen; Static Electricity

In order to provide a solution for the poor aqueous solubility and poor bioavailability of curcumin, we present the synthesis and characteristic features of water-soluble curcumin hydrated nanoparticles (CNPs). They are stable and nearly monodisperse in the aqueous phase where the keto form of curcumin self-assembles into spherical CNPs, which are highly sensitive to temperature and pH variations. The CNPs are quite stable up to 40 °C and at neutral pH. A higher temperature range reduces their hydration and makes them unstable, thereby disintegrating them into smaller aggregates. Similarly, a higher pH converts the keto form of CNPs into the enol form by promoting their interparticle fusions driven by hydrogen bonding with a remarkable color change from yellow to bright orange-red which demonstrates their excellent photophysical behavior. The stable keto form CNPs are highly efficient nonreactors for the in situ synthesis of Au, Ag, and Pd NPs which are simultaneously entrapped in curcumin aggregates, thus promoting the metal NP carrying ability of curcumin aggregates. The CNPs also demonstrate their excellent dose-dependent biocompatibility with blood cells. A concentration range up to 5 mM of CNPs is quite safe for their applications in biological systems.

Topics: Blood Cells; Curcumin; Drug Carriers; Hemolysis; Humans; Hydrogen Bonding; Hydrogen-Ion Concentration; Nanoparticles; Temperature

At present, the chemotherapy of advanced inoperable liver cancer is limited with serious side effects. Curcumin possesses multiple cancer preventive activities and low safety concerns. However, its poor solubility and instability in water pose significant pharmacological barriers to its clinical application. In this study, we presented a novel delivery system - the glycyrrhetinic acid modified curcumin-loaded cationic liposomes (GAMCLCL) and investigated its antitumor activities on HepG2 cells in vitro and in H22 tumor-bearing mice. The experimental results demonstrated that GAMCLCL was a cationic liposome and could be Intravenous administration. Compared to free curcumin, GAMCLCL exhibited stronger antitumor activities in vitro and in vivo. The antitumor results of GAMCLCL after intravenous administration were very similar to those after intratumoral administration. The main activities of GAMCLCL and curcumin included inhibition of HepG2 cell proliferation, inhibition of tumor growth, reduction of tumor microvascular density, down-regulation of the expression of VEGF protein, and up-regulation of the expression of Caspases3 protein in H22 tumor tissues. Furthermore, GAMCLCL improved the parameters of WBC, RBC, ALT, CRE, LDH of H22 tumor-bearing mice. Curcumin is a nontoxic natural compound with definite antitumor activities, its antitumor effects can be enhanced by preparation of GAMCLCL.

Topics: Amines; Animals; Antineoplastic Agents; Apoptosis; Cations; Cell Proliferation; Curcumin; Dose-Response Relationship, Drug; Drug Carriers; Erythrocytes; Glycyrrhetinic Acid; Hemolysis; Hep G2 Cells; Humans; Liposomes; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred Strains; Tissue Distribution; Xenograft Model Antitumor Assays

Peptide nanostructure has been widely explored for drug-delivery systems in recent studies. Peptides possess comparatively lower cytotoxicity and are more efficient than polymeric carriers. Here, we propose a peptide nanorod system, composed of an amphiphilic oligo-peptide RH

Topics: Animals; Antineoplastic Agents; Apoptosis; Biocompatible Materials; Cell Line, Tumor; Curcumin; Drug Carriers; HeLa Cells; Hemolysis; Humans; Nanotubes; Neoplasms; Oligopeptides; Phenylalanine; Surface-Active Agents; Zebrafish

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Chitosan; Contrast Media; Curcumin; Drug Carriers; Drug Liberation; Drug Stability; Erythrocytes; Fluorocarbons; Hemolysis; Humans; Nanoparticles; Particle Size; Sonication; Spectroscopy, Fourier Transform Infrared

This work delineates the synthesis of curcumin (Ccm) and methotrexate (MTX) conjugated biopolymer stabilized AuNPs (MP@Alg-Ccm AuNPs). The dual drug conjugated nano-vector was characterized by FTIR, (1)H NMR and UV-vis spectroscopic techniques. Hydrodynamic diameter and surface charge of the AuNPs were determined by DLS analysis and the spherical particles were visualized by TEM. MP@Alg-Ccm AuNPs exhibited improved cytotoxic potential against C6 glioma and MCF-7 cancer cell lines and was found to be highly hemocompatible. MP@Alg-Ccm AuNPs also exhibited active targeting efficiency against MCF-7 cancer cells due to the presence of "antifolate" drug MTX. Thus MP@Alg-Ccm AuNPs may find potential application in targeted combination chemotherapy for the treatment of cancer. The study is also interesting from the synthetic point of view because, here generation of AuNPs was done using "green chemical" alginate and dual drug conjugated AuNPs were created in two simple reaction steps using "green solvent" water.

Topics: Alginates; Animals; Biological Transport; Curcumin; Drug Carriers; Drug Stability; Glucuronic Acid; Gold; Hemolysis; Hexuronic Acids; Humans; MCF-7 Cells; Metal Nanoparticles; Methotrexate; Rats

Curcumin, a component in spice turmeric, is renowned to possess anti-cancer therapeutic potential. However, low aqueous solubility and instability of curcumin which subsequently affects its bioavailability pose as major impediments in its translation to clinical application. In this regard, we focused on conjugating hydrophobic curcumin to the hydrophilic backbone of dextran via succinic acid spacer to design a pro-drug. The structural confirmation of the conjugates was carried out using FTIR and (1)H NMR spectroscopy. Critical micelle measurement affirmed the micelle formation of the pro-drug in aqueous media. The size distribution and zeta potential of the curcumin-dextran (Cur-Dex) micelles were determined using dynamic light scattering technique. The micellar architecture bestowed curcumin negligible susceptibility to degradation under physiological conditions along with enhanced aqueous solubility. Biocompatibility of the micelles was proved by the blood component aggregation and plasma protein interaction studies. In vitro release studies demonstrated the pH sensitivity release of curcumin which is conducive to the tumour micro environment. Profound cytotoxic effects of Cur-Dex micelles in C6 glioma cells were observed from MTT and Live/Dead assay experiments. Moreover, enhanced cellular internalization of the Cur-Dex micelles compared to free curcumin in the cancer cells was revealed by fluorescence microscopy. Our study focuses on the feasibility of Cur-Dex micelles to be extrapolated as promising candidates for safe and efficient cancer therapy.

Topics: Antineoplastic Agents; Blood Cells; Cell Line, Tumor; Cells, Cultured; Curcumin; Dextrans; Hemolysis; Humans; Hydrogen-Ion Concentration; Micelles; Prodrugs

Many hydrophobic drugs encounter severe bioavailability issues owing to their low aqueous solubility and limited cellular uptake. We have designed a series of amphiphilic polyaspartamide polyelectrolytes (PEs) that solubilize such hydrophobic drugs in aqueous medium and enhance their cellular uptake. These PEs were synthesized through controlled (∼20 mol %) derivatization of polysuccinimide (PSI) precursor polymer with hydrophobic amines (of varying alkyl chain lengths, viz. hexyl, octyl, dodecyl, and oleyl), while the remaining succinimide residues of PSI were opened using a protonable and hydrophilic amine, 2-(2-amino-ethyl amino) ethanol (AE). Curcumin (Cur) was employed as a representative hydrophobic drug to explore the drug-delivery potential of the resulting PEs. Unprecedented enhancement in the aqueous solubility of Cur was achieved by employing these PEs through a rather simple protocol. In the case of PEs containing oleyl/dodecyl residues, up to >65000× increment in the solubility of Cur in aqueous medium could be achieved without requiring any organic solvent at all. The resulting suspensions were physically and chemically stable for at least 2 weeks. Stable nanosized polyelectrolyte complexes (PECs) with average hydrodynamic diameters (DH) of 150-170 nm (without Cur) and 220-270 nm (after Cur loading) were obtained by using submolar sodium polyaspartate (SPA) counter polyelectrolyte. The zeta potential of these PECs ranged from +36 to +43 mV. The PEC-formation significantly improved the cytocompatibility of the PEs while affording reconstitutable nanoformulations having up to 40 wt % drug-loading. The Cur-loaded PECs were readily internalized by mammalian cells (HEK-293T, MDA-MB-231, and U2OS), majorly through clathrin-mediated endocytosis (CME). Cellular uptake of Cur was directly correlated with the length of the alkyl chain present in the PECs. Further, the PECs significantly improved nuclear transport of Cur in cancer cells, resulting in their death by apoptosis. Noncancerous cells were completely unaffected under this treatment.

Topics: Antineoplastic Agents; Cell Membrane Permeability; Cell Survival; Curcumin; Drug Carriers; Drug Delivery Systems; Hemolysis; Humans; Hydrophobic and Hydrophilic Interactions; Nanocomposites; Neoplasms; Polyelectrolytes; Solubility

One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer.

Topics: Abdominal Neoplasms; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Colonic Neoplasms; Curcumin; Docetaxel; Drug Carriers; Drug Screening Assays, Antitumor; Flow Cytometry; Hemolysis; Humans; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Microspheres; Molecular Weight; Nanofibers; Nanoparticles; Neoplasm Metastasis; Poloxamer; Polymers; Spectroscopy, Fourier Transform Infrared; Taxoids; Thermogravimetry; X-Ray Diffraction

α-hemolysin (Hla) is a self-assembling extracellular protein secreted as a soluble monomer by most Staphylococcus aureus strains and is an essential virulence factor for the pathogenesis of various S. aureus infections. Here, we show that curcumin (CUR), a natural compound with weak anti-S. aureus activity, can inhibit the hemolysis induced by Hla. Molecular dynamics simulations, free energy calculations, and mutagenesis assays were further employed for the Hla-CUR complex to determine the mechanism of such inhibition. The analysis of this combined approach indicated that the direct binding CUR to Hla blocks the conformational transition of Hla from the monomer to the oligomer, leading to an inhibition of Hla hemolytic activity. We also found that the addition of CUR significantly attenuated Hla-mediated injury of human alveolar cell (A549) co-cultured with S. aureus. The in vivo data further demonstrated that treatment with CUR protects mice from pneumonia caused by S. aureus, including methicillin-resistant strains (MRSA). These findings suggest that CUR inhibits the pore-forming activity of Hla through a novel mechanism, which would pave the way for the development of new and more effective antibacterial agents to combat S. aureus pneumonia.

Topics: Animals; Anti-Bacterial Agents; Bacterial Toxins; Curcumin; Female; Hemolysin Proteins; Hemolysis; Methicillin Resistance; Mice; Mice, Inbred C57BL; Pneumonia, Staphylococcal; Protective Agents; Staphylococcus aureus; Virulence Factors

This paper elucidates the development of a curcumin cross-linked collagen aerogel system with controlled anti-proteolytic activity and pro-angiogenic efficacy. The results of this study showed that in situ cross-linking of curcumin with collagen leads to the development of aerogels with enhanced physical and mechanical properties. The integrity of collagen after cross-linking with curcumin was studied via FTIR spectroscopy. The results confirmed that the cross-linking with curcumin did not induce any structural changes in the collagen. The curcumin cross-linked collagen aerogels exhibited potent anti-proteolytic and anti-microbial activity. Scanning electron and atomic force microscopic analysis of curcumin cross-linked collagen aerogels showed a 3D microstructure that enhanced the adhesion and proliferation of cells. The highly organized geometry of collagen-curcumin aerogels enhanced the permeability and water-retaining ability required for the diffusion of nutrients that aid cellular growth. The pro-angiogenic properties of collagen-curcumin aerogels were ascribed to the cumulative effect of the nutraceutical and the collagen molecule, which augmented the restoration of damaged tissue. Further, these aerogels exhibited controlled anti-proteolytic activity, which makes them suitable 3D scaffolds for biomedical applications. This study provides scope for the development of biocompatible and bioresorbable collagen aerogel systems that use a nutraceutical as a cross-linker for biomedical applications.

Topics: Animals; Anti-Bacterial Agents; Biocompatible Materials; Chick Embryo; Chorioallantoic Membrane; Collagen; Cross-Linking Reagents; Curcumin; Dietary Supplements; Female; Hemolysis; Humans; Hydrogels; Kinetics; Materials Testing; Neovascularization, Physiologic; Permeability; Porosity; Rats; Rats, Wistar; Rheology; Stress, Mechanical; Tensile Strength; Tissue Scaffolds; Wound Healing

The present study deals with the toxicity assessment of NBDMCA in vitro using red cell model and in vivo using rat model. Hemolysis was used as toxicity index in red blood cells. Different concentrations of NBDMCA viz., 20, 40, 60, 80, 100μg/ml in PBS were incubated with the red blood cells of rat. NBDMCA was found to induce less than 3% hemolysis in intact erythrocytes which was far lesser than the accepted threshold of 5%. Hematological cum biochemical parameters along with histopathological analysis and hemolysis were used as toxicity indices in rats. Whole blood of the NBDMCA-treated rats and control rats were analyzed for hematological parameters: erythrocyte count, leukocyte count, leukocyte differential count, hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH) using fully automated hematology analyzer. All hematological parameters analyzed were within the normal values in both the groups. Plasma samples were analyzed for biochemical parameters including glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (Cre), albumin (Alb), total protein (TP), calcium (Ca) and phosphorus (P) using fully automated biochemistry analyzer. Invariably, all the biochemical parameters are significantly similar in both the groups. Gross examination of vital organs like lung, heart, kidney, spleen and brain reveals no detectable abnormalities in NBDMCA-treated animals. Internal organs like heart, brain, lung, liver, spleen and kidneys of the experimental animals were collected and fixed in 10% formalin, processed in vacuum infiltration tissue processor, embedded with paraffin wax and sectioned at approximately 5μm thick, stained with hematoxylin and eosin. The sections were examined and imaged through light microscopy. NBDMCA did not produce any significant changes in the histoarchitecture of all the organs studied. Heart, aorta, brain, lung, liver, kidney and spleen showed normal pathology report. The histopathological data correlated with the biochemical results indicating normal hepatocellular and nephrotic function. Our investigation clearly revealed that NBDMCA is hemocompatible in vitro and also safe to vital organs in vivo. We conclude that NBDMCA is non-toxic and safe and can be promoted as an ideal therapeutic tool for human use.

Topics: Administration, Intravenous; Animals; Cells, Cultured; Curcumin; Diarylheptanoids; Erythrocyte Count; Erythrocyte Indices; Erythrocytes; Hemolysis; Leukocyte Count; Male; Nanoparticles; Rats, Wistar

The purpose of this study was to compare the antioxidant capacities of seven natural pigments including the fat-soluble pigments curcumin, lycopene, lutein and β-carotene and water-soluble pigments--betalain, capsanthin and cyanidin-3-rutinoside relative to a commonly-used synthetic food antioxidant BHA. The antioxidant capacities of seven pigments and BHA were evaluated based on their ability to quench several free radicals, including DPPH, ABTS, O2(·-), H2O2 as well as using FRAP assay. Specifically, curcumin and cyanidin-3-rutinoside, which showed the highest antioxidant capacities, were further investigated using a chicken erythrocyte model. After separating pretreatments of the two pigments, AAPH was added to the erythrocyte-pigment medium to induce oxidative stress. Then the attenuation effects of the two pigments on AAPH-induced oxidative damage in chicken erythrocytes were assessed. It was found that both curcumin and cyanidin-3-rutinoside significantly attenuated apoptosis and hemolysis, decreased MDA content, and increased T-SOD activity in a time- and dose- dependent manner.

Topics: Amidines; Animals; Antioxidants; Chickens; Curcumin; Erythrocytes; Free Radical Scavengers; Hemolysis; Lipid Peroxidation; Pigments, Biological

Novel poly(anhydride-ester)-b-poly(ethylene glycol) copolymers (PAE-b-PEGs) were synthesized by esterization of methyl poly(ethylene glycol) and poly(anhydride-ester), which were obtained by the melt polycondensation of alpha,omega-acetic anhydride-terminated poly(L-lactic acid), and characterized by 1H-NMR and gel permeation chromatography. The two poly(anhydride-ester)-b-poly(ethylene glycols) (denoted as PAE-b-PEG2k and PAE-b-PEG5k) thus obtained can self-assemble in water to form micelles with hydrodynamic diameters of 92.5 and 97.5 nm above their critical micelle concentrations of 3.78 and 2.36 microg/mL, respectively. The curcumin-loaded PAE-b-PEG2k and PAE-b-PEG5k micelles were prepared by the solid dispersion method, and they could encapsulate approximately 7% (w/w) curcumin. The diameters of the micelles were stable for 5 days. Curcumin is released faster from the micelles at pH 5.0 than at pH 7.4. Curcumin is released from the micelles at a fast rate during the initial 12 h, followed by a zero-order release during the subsequent 200 h, both at pH 5.0 and 7.4. The IC50 values of the curcumin-loaded PAE-b-PEG2k and PAE-b-PEG5k micelles against HeLa cells are 12.41 and 15.31 microg/mL, respectively, which is lower than that of free curcumin (25.90 microg/mL). The PAE-b-PEG2k micelles are taken up faster than the PAE-b-PEG5k micelles by HeLa cells. Curcumin-loaded micelles can induce G2/M phase cell cycle arrest and apoptosis of HeLa cells.

Topics: Animals; Cell Cycle; Cell Death; Curcumin; Endocytosis; Esters; HeLa Cells; Hemolysis; Humans; Hydrodynamics; Kinetics; Lactic Acid; Magnetic Resonance Spectroscopy; Micelles; Microscopy, Electron, Transmission; Polyanhydrides; Polyesters; Polyethylene Glycols; Polymers; Rats; Rats, Sprague-Dawley; Spectrometry, Fluorescence; Surface-Active Agents; X-Ray Diffraction

Colon cancer is the third most leading causes of death due to cancer worldwide and the chemo drug 5-fluorouracil's (5-FU) applicability is limited due to its non-specificity, low bioavailability and overdose. The efficacy of 5-FU in colon cancer chemo treatment could be improved by nanoencapsulation and combinatorial approach. In the present study curcumin (CUR), a known anticancer phytochemical, was used in combination with 5-FU and the work focuses on the development of a combinatorial nanomedicine based on 5-FU and CUR in N,O-carboxymethyl chitosan nanoparticles (N,O-CMC NPs). The developed 5-FU-N,O-CMC NPs and CUR-N,O-CMC NPs were found to be blood compatible. The in vitro drug release profile in pH 4.5 and 7.4 showed a sustained release profile over a period of 4 days. The combined exposure of the nanoformulations in colon cancer cells (HT 29) proved the enhanced anticancer effects. In addition, the in vivo pharmacokinetic data in mouse model revealed the improved plasma concentrations of 5-FU and CUR which prolonged up to 72 h unlike the bare drugs. In conclusion, the 5-FU and CUR released from the N,O-CMC NPs produced enhanced anticancer effects in vitro and improved plasma concentrations under in vivo conditions.

Topics: Animals; Antineoplastic Agents; Area Under Curve; Blood Coagulation; Cell Cycle; Cell Line; Cell Line, Tumor; Chitosan; Colonic Neoplasms; Curcumin; Drug Carriers; Drug Delivery Systems; Female; Fluorouracil; Hemolysis; HT29 Cells; Humans; Hydrogen-Ion Concentration; Membrane Potentials; Mice; Nanoparticles; Spectroscopy, Fourier Transform Infrared

In this study, a novel linolenic acid-modified poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer was prepared through radical addition, ring-opening polymerization, and N-acylation reactions. Its structure was characterized by (1)H NMR and GPC. Micelles were developed by thin-film hydration and used as a delivery system for curcumin with high drug loading capacity of 12.80% and entrapment efficiency of 98.53%. The water solubility of curcumin was increased to 2.05 mg/mL, which was approximately 1.87×10(5) times higher than that of free curcumin. The micelles were spherical shape with an average diameter of 20.8±0.8 nm. X-ray diffraction and FT-IR studies suggested that curcumin existed in the polymeric matrices under π-π conjugation and hydrogen bond interaction with the copolymer. In vitro drug release studies indicated that the curcumin release from linolenic acid-modified copolymer micelles met controlled release, and its release rate was less than that from the linolenic acid-unmodified copolymer micelles. Cytotoxicities against Hela and A-549cells demonstrated that the additional π-π conjugation could affect curcumin's anticancer activity through reducing its release from micelles. Hemolysis test and intravenous irritation test results revealed that the linolenic acid-modified copolymer was safe for intravenous injection. The plasma AUC0-∞ and MRT0-∞ of curcumin-loaded linolenic acid-conjugated poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer micelles were 2.75- and 3.49-fold higher than that of control solution, respectively. The CLz was also decreased by 2.75-fold. So, this linolenic acid-modified copolymer might be a carrier candidate for curcumin delivery.

Topics: alpha-Linolenic Acid; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Curcumin; Drug Carriers; Drug Liberation; Erythrocytes; Ethylene Glycols; HeLa Cells; Hemolysis; Humans; Male; Micelles; Particle Size; Polyesters; Rabbits; Rats, Sprague-Dawley; Surface Properties; Tissue Distribution

Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.

Topics: Animals; Cell Death; Cell Survival; Curcumin; Drug Delivery Systems; Endocytosis; Folic Acid; Hemolysis; Hep G2 Cells; Humans; Irritants; Lactic Acid; Male; MCF-7 Cells; Micelles; Microscopy, Fluorescence; Neoplasms; Particle Size; Polyesters; Polyethylene Glycols; Polymers; Rabbits; Rats; Static Electricity; Surface-Active Agents

Curcumin has been widely investigated for its myriad cellular effects resulting in reduced proliferation of various eukaryotic cells including cancer cells and the human malaria parasite Plasmodium falciparum. Studies with human cancer cell lines HT-29, Caco-2, and MCF-7 suggest that curcumin can bind to tubulin and induce alterations in microtubule structure. Based on this finding, we investigated whether curcumin has any effect on P. falciparum microtubules, considering that mammalian and parasite tubulin are 83% identical. IC50 of curcumin was found to be 5 µM as compared to 20 µM reported before. Immunofluorescence images of parasites treated with 5 or 20 µM curcumin showed a concentration-dependent effect on parasite microtubules resulting in diffuse staining contrasting with the discrete hemispindles and subpellicular microtubules observed in untreated parasites. The effect on P. falciparum microtubules was evident only in the second cycle for both concentrations tested. This diffuse pattern of tubulin fluorescence in curcumin treated parasites was similar to the effect of a microtubule destabilizing drug vinblastine on P. falciparum. Molecular docking predicted the binding site of curcumin at the interface of alpha and beta tubulin, similar to another destabilizing drug colchicine. Data from predicted drug binding is supported by results from drug combination assays showing antagonistic interactions between curcumin and colchicine, sharing a similar binding site, and additive/synergistic interactions of curcumin with paclitaxel and vinblastine, having different binding sites. This evidence suggests that cellular effects of curcumin are at least, in part, due to its perturbing effect on P. falciparum microtubules. The action of curcumin, both direct and indirect, on P. falciparum microtubules is discussed.

Topics: Binding Sites; Colchicine; Curcumin; Dose-Response Relationship, Drug; Drug Synergism; Erythrocytes; Hemolysis; Humans; Microtubules; Molecular Docking Simulation; Paclitaxel; Plasmodium falciparum; Protein Binding; Protein Conformation; Protein Multimerization; Tubulin; Tubulin Modulators; Vinblastine

Pyrazolealdehydes (4a-d), Knoevenagel's condensates (5a-d) and Schiff's bases (6a-d) of curcumin-I were synthesized, purified and characterized. Hemolysis assays, cell line activities, DNA bindings and docking studies were carried out. These compounds were lesser hemolytic than standard drug doxorubicin. Minimum cell viability (MCF-7; wild) observed was 59% (1.0 μg/mL) whereas the DNA binding constants ranged from 1.4×10(3) to 8.1×10(5) M(-1). The docking energies varied from -7.30 to -13.4 kcal/mol. It has been observed that DNA-compound adducts were stabilized by three governing forces (Van der Wall's, H-bonding and electrostatic attractions). It has also been observed that compounds 4a-d preferred to enter minor groove while 5a-d and 6a-d interacted with major grooves of DNA. The anticancer activities of the reported compounds might be due to their interactions with DNA. These results indicated the bright future of the reported compounds as anticancer agents.

Topics: Antineoplastic Agents; Cell Survival; Curcumin; DNA; Hemolysis; Humans; MCF-7 Cells; Molecular Docking Simulation; Neoplasms; Pyrazoles; Schiff Bases

The anti-inflammatory and antiproliferative agent curcumin has poor oral bioavailability and solubility in plasma. Liposomal formulations have therefore been developed, but the toxicity of these preparations is not yet established. We investigated the influence of free and liposomally formulated curcumin on human red blood cell (RBC) morphology in vitro.. EDTA-buffered whole blood from two healthy individuals was incubated with different concentrations (1, 10, 100 μg/ml) of free or liposomal curcumin. RBC morphology and mean cellular volume (MCV) were examined at up to 4 hours of incubation.. Dose-dependent echinocyte formation was observed after incubation with free, and liposomal curcumin, with a threshold concentration of 10 μg/ml and peak effect after 30 minutes. A concomitant increase in mean cellular volume was detectable.. Curcumin and liposomal curcumin cause dose-dependent changes in the shape of RBCs. This effect may represent an early sign of dose-limiting toxicity following intravenous administration.

Topics: Curcumin; Erythrocytes; Hemolysis; Humans; In Vitro Techniques; Liposomes

Clinical application of curcumin has been limited due to poor aqueous solubility and consequently minimal systemic bioavailability. We investigated the preparation of curcumin-loaded micelles based on amphiphilic Pluronic/Polycaprolactone (Pluronic/PCL) block copolymer, which proved to be efficient in enhancing curcumin's aqueous solubility. Curcumin-loaded micelles of size below 200 nm was characterized by dynamic light scattering and transmission electron microscopy. The critical micelle concentration (CMC) of the amphiphilic polymer was determined using pyrene as a fluorescent probe. Hemolysis and aggregation studies were investigated to evaluate the blood compatibility of the micelles. Sodium dodecyl sulphate polyacrylamide gel electrophoresis was performed to study the stability of the micelles toward plasma proteins. In vitro cytotoxicity and cellular uptake of the curcumin-loaded micelles were demonstrated in colorectal adenocarcinoma (Caco2) cells. The results indicated that Pluronic/PCL micelles could be a promising candidate for curcumin delivery to cancer cells.

Topics: Adenocarcinoma; Antineoplastic Agents; Blood Platelets; Caco-2 Cells; Colorectal Neoplasms; Curcumin; Drug Carriers; Erythrocytes; Hemolysis; Humans; Micelles; Particle Size; Poloxamer

Cinnamaldehyde, its derivatives and curcumin are reported to have strong antifungal activity. In this work we report and compare anticandidal activity of curcumin (CUR) and α-methyl cinnamaldehyde (MCD) against 38 strains of Candida (3; standard, fluconazole sensitive, 24; clinical, fluconazole sensitive, 11; clinical, fluconazole resistant). The minimum inhibitory concentrations (MIC₉₀) of CUR ranged from 250 to 650 μg/ml for sensitive strains and from 250 to 500 μg/ml for resistant strains. MIC₉₀ of MCD varied between 100 and 250 μg/ml and 100-200 μg/ml for sensitive and resistant strains, respectively. Higher activity of MCD as compared to CUR was further reinforced by spot assays and growth curve studies. At their respective MIC₉₀ values, in the presence of glucose, average inhibition of H+-efflux caused by CUR and MCD against standard, clinical and resistant isolates was 24%, 31%, 32% and 54%, 52%, 54%, respectively. Inhibition of H+-extrusion leads to intracellular acidification and cell death, average pHi for control, CUR and MCD exposed cells was 6.68, 6.39 and 6.20, respectively. Scanning electron micrographs of treated cells show more extensive damage in case of MCD. Haemolytic activity of CUR and MCD at their highest MIC was 11.45% and 13.00%, respectively as against 20% shown by fluconazole at typical MIC of 30 μg/ml. In conclusion, this study shows significant anticandidal activity of CUR and MCD against both azole-resistant and sensitive clinical isolates, MCD is found to be more effective.

Topics: Acrolein; Antifungal Agents; Candida; Curcumin; Drug Resistance; Erythrocytes; Fluconazole; Hemolysis; Humans; Plant Extracts

Curcuminoids are poorly water-soluble compounds with promising antimalarial activity. To overcome some of the drawbacks of curcuminoids, we explored the potential of liposomes for the intravenous delivery of curcuminoids in a model of mouse malaria. The curcuminoids-loaded liposomes were formulated from phosphatidylcholine (soy PC) by the thin-film hydration method. Antimalarial activity of curcuminoids-loaded liposomes alone and in combination with α/β arteether when administered intravenously, was evaluated in Plasmodium berghei infected mice. Animals treated with curcuminoids-loaded liposomes showed lower parasitemia and higher survival when compared to control group (no treatment). Importantly, the combination therapy of curcuminoids-loaded liposomes (40 mg/kg body wt) along with α/β arteether (30 mg/kg body wt) was able to not only cure infected mice but also prevented recrudescence. These data suggest that curcuminoids-loaded liposomes may show promise as a formulation for anti-malarial therapy.

Topics: Animals; Antimalarials; Artemisinins; Curcuma; Curcumin; Diarylheptanoids; Disease Models, Animal; Hemolysis; Humans; Liposomes; Malaria; Mice; Phytotherapy; Plant Extracts; Plant Roots; Plasmodium berghei; Polyphenols

The present study investigates the protective effects of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity using various animal models with biochemical parameters like serum marker enzymes and antioxidants in target tissues. In addition, liver and cardiac histoarchitecture changes were also studied. Curcumin treatment inhibited carrageenin and albumin induced edema, cotton pellet granuloma formation. The increased relative weight of liver and heart in CCl(4) induced liver injury and isoproterenol induced cardiac necrosis were also reduced by curcumin treatment. Elevated serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) increased lipid peroxidation, decreased gluthione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in edematous, granulomatus, liver and heart tissues during inflammation, liver injury and cardiac necrosis, respectively. Curcumin treatment reversed all these above mentioned biochemical changes significantly in all animal models studied. Even histoarchitecture alterations observed in liver injury and cardiac necrosis observed were partially reversed (improved) by curcumin treatments. In in vitro experiments too curcumin inhibited iron catalyzed lipid peroxidation in liver homogenates, scavenged nitric oxide spontaneously generated from nitroprusside and inhibited heat induced hemolysis of rat erythrocytes. The present in vitro and in vivo experimental findings suggest the protective effect of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity in rats.

Topics: Animals; Antioxidants; Biomarkers; Body Weight; Chemical and Drug Induced Liver Injury; Curcumin; Edema; Erythrocytes; Female; Granuloma, Foreign-Body; Heart; Hemolysis; In Vitro Techniques; Lipid Peroxidation; Liver; Liver Function Tests; Male; Myocardium; Necrosis; Organ Size; Rats; Rats, Wistar

The interest in nanosuspensions by the pharmaceutical industry is increasing given several nanosuspension products currently on the market for poorly soluble drugs. In this study, a novel dosage form for curcumin (CUR), CUR nanosuspension (CUR-NS), was successfully prepared by high pressure homogenization to improve CUR's cytotoxicity, as well as improve its application via intravenous injection. Characterization of the CUR-NS was evaluated by morphology, size, zeta potential, solubility, dissolution rate, and crystal state of drug. The nanoparticles for CUR-NS presented a sphere-like shape under transmission electron microscopy with an average diameter of 250.6 nm and the zeta potential of CUR-NS was -27.92 mV. Solubility and dissolution rate of CUR in the form of CUR-NS were significantly increased due to the small particle size and the crystalline state of CUR was preserved to increase its stability against degradation. Superior cytotoxicity in Hela and MCF-7 cells was obtained for CUR-NS compared with CUR solution. The safety evaluation showed that, compared with the CUR solution, CUR-NS provided less local irritation and phlebitis risks, lower rate of erythrocyte hemolysis. These findings suggest that CUR-NS may represent a promising new drug formulation for intravenous administration in the treatment of certain cancers.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Chemical Phenomena; Chemistry, Pharmaceutical; Curcumin; Drug Stability; Erythrocytes; Freeze Drying; HeLa Cells; Hemolysis; Humans; Injections, Intravenous; Microscopy, Electron, Transmission; Nanoparticles; Nanotechnology; Neoplasms; Rabbits; Suspensions

In order to clarify the contribution of phenolic and enolic hydroxyl group to the antioxidant capacity of feruloylacetone, a model compound of half-curcumin, 6-(p-hydroxy-m-methoxyphenyl)-5-hexene-2,4-dione (FT), 6-(p-benzyloxy-m-methoxyphenyl)-5-hexene-2,4-dione (BMFT), 6-(m,p-dihydroxyphenyl)-5-hexene-2,4-dione (DDFT), 6-(p-hydroxy-m-methoxyphenyl)hexane-2,4-dione (DHFT), 6-(p-hydroxy-m-methoxyphenyl)-5-hexene-2,4-diol (THFT), and ethyl 2-(p-hydroxy-m-methoxybenzylidene)-3-oxobutanoate (EOFT) were synthesized. The radical-scavenging abilities of these compounds were tested by trapping 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+·)), 2,2'-diphenyl-1-picrylhydrazyl (DPPH), and galvinoxyl radicals. The reductive capacities were screened by quenching singlet oxygen and by inhibiting the oxidation of linoleic acid. They were also employed to inhibit the oxidation of DNA mediated by hydroxyl radical and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH). In addition, they were applied to protect erythrocytes against AAPH- and hemin-induced hemolysis. The obtained results revealed that the antioxidant capacity of half-curcumin was derived from the phenolic-OH and the conjugated linkage between phenolic and enolic-OH. The enolic-OH itself cannot trap radicals.

Topics: Acetone; Amidines; beta Carotene; Copper; Curcumin; DNA; Erythrocytes; Free Radical Scavengers; Free Radicals; Glutathione; Hemin; Hemolysis; Humans; Linoleic Acids; Oxidation-Reduction; Structure-Activity Relationship; Styrenes

A nano formulation of curcumin loaded biodegradable thermoresponsive chitosan-g-poly (N-isopropylacrylamide) co-polymeric nanoparticles (TRC-NPs) (150 nm) were prepared by ionic cross-linking method and characterized. The in vitro drug release was prominent at above LCST. Cytocompatibility of TRC-NPs (100-1000 μg/ml) on an array of cell line is proved by MTT assay. The drug loaded TRC-NPs showed specific toxicity on cancer cells. The cell uptake studies were confirmed by fluorescent microscopy. Flowcytometric analysis of curcumin loaded TRC-NPs showed increased apoptosis on PC3 cells. These results indicated that TRC-NPs could be a potential nanovehicle for curcumin drug delivery.

Topics: Acrylamides; Animals; Apoptosis; Biocompatible Materials; Cell Line; Cell Survival; Chitosan; Curcumin; Drug Carriers; Drug Delivery Systems; Hemolysis; Humans; Mice; Nanoparticles; Particle Size

In this work we prepared and evaluated the curcumin loaded fibrinogen nanoparticles (CRC-FNPs) as a novel drug delivery system for cancer therapy. These novel CRC-FNPs were prepared by a two-step co-acervation method using calcium chloride as the cross-linker. The prepared nanoparticles were characterized using dynamic light scattering (DLS), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry (TG), differential thermal analysis (DTA) and X-ray diffraction (XRD) studies. DLS studies showed that the particle size of CRC-FNPs was in the range of 150-200 nm. The loading efficiency (LE) and in vitro drug release were studied using UV spectrophotometer. The LE was found to be 90%. The cytotoxicity was studied using L929 (mouse fibroblast), PC3 (prostate) and MCF7 (breast) cancer cell lines by MTT assay, which confirmed that CRC-FNPs were comparatively non toxic to L929 cell line while toxic to PC3 and MCF7 cancer cells. Cellular uptake of CRC-FNPs studied using L929, MCF-7 and PC3 cells monitored by fluorescent microscopy, demonstrated significant internalization and retention of nanoparticles inside the cells. The preferential accumulation of curcumin within the cancer cells were also confirmed by flowcytometry based uptake studies. The apoptosis assay showed increased apoptosis on MCF-7 compared to L929 cells. The blood compatibility of CRC-FNPs throws light on the fact that it is possible to administer the prepared nanoformulation intravenously. The results indicated that CRC-FNPs could be a promising therapeutic agent for cancer treatment.

Topics: Animals; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line; Cell Line, Tumor; Curcumin; Drug Delivery Systems; Female; Fibrinogen; Hemolysis; Humans; In Vitro Techniques; Male; Materials Testing; Mice; Nanocapsules; Nanotechnology; Particle Size; Prostatic Neoplasms

Recent studies report curcumin nanoformulation(s) based on polylactic-co-glycolic acid (PLGA), β-cyclodextrin, cellulose, nanogel, and dendrimers to have anticancer potential. However, no comparative data are currently available for the interaction of curcumin nanoformulations with blood proteins and erythrocytes. The objective of this study was to examine the interaction of curcumin nanoformulations with cancer cells, serum proteins, and human red blood cells, and to assess their potential application for in vivo preclinical and clinical studies.. The cellular uptake of curcumin nanoformulations was assessed by measuring curcumin levels in cancer cells using ultraviolet-visible spectrophotometry. Protein interaction studies were conducted using particle size analysis, zeta potential, and Western blot techniques. Curcumin nanoformulations were incubated with human red blood cells to evaluate their acute toxicity and hemocompatibility.. Cellular uptake of curcumin nanoformulations by cancer cells demonstrated preferential uptake versus free curcumin. Particle sizes and zeta potentials of curucumin nanoformulations were varied after human serum albumin adsorption. A remarkable capacity of the dendrimer curcumin nanoformulation to bind to plasma protein was observed, while the other formulations showed minimal binding capacity. Dendrimer curcumin nanoformulations also showed higher toxicity to red blood cells compared with the other curcumin nanoformulations.. PLGA and nanogel curcumin nanoformulations appear to be very compatible with erythrocytes and have low serum protein binding characteristics, which suggests that they may be suitable for application in the treatment of malignancy. These findings advance our understanding of the characteristics of curcumin nanoformulations, a necessary component in harnessing and implementing improved in vivo effects of curcumin.

Topics: Analysis of Variance; Blood Proteins; Cell Line, Tumor; Curcumin; Drug Carriers; Erythrocytes; Hemolysis; Humans; Lactic Acid; Male; Materials Testing; Nanogels; Nanostructures; Particle Size; Polyethylene Glycols; Polyethyleneimine; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Protein Binding; Serum Albumin; Spectrophotometry, Ultraviolet

In this study, doxorubicin (DOX)-loaded long circulating liposomes combined with curcumin (CUR) (DOX-CUR-LCLs) were successfully prepared as a novel formulation for cancer treatment. The particle size and distribution, zeta potential, drug loading capacity, and entrapment efficiency (EE) of the preparation were characterized. The in vitro anti-tumor activities of DOX-CUR-LCLs and DOX-LCLs against A549 cells were then evaluated and compared with that of free DOX. Cytotoxicity evaluation showed that DOX-CUR-LCLs had a significantly higher antitumor activity than other DOX preparations. These results suggest that novel DOX-CUR-LCLs, combination of DOX and CUR administered in long-circulating liposomes, could improve antitumor activity.

Topics: Animals; Antibiotics, Antineoplastic; Blood Vessels; Cell Survival; Chemistry, Pharmaceutical; Curcumin; Doxorubicin; Drug Compounding; Ear, External; Hemolysis; In Vitro Techniques; Irritants; Liposomes; Rabbits; Skin

In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Curcumin; Drug Compounding; Drug Stability; Glycerides; Hemolysis; Humans; Kinetics; Lipids; Malaria; Mice; Microscopy, Electron, Scanning; Nanoparticles; Particle Size; Plasmodium berghei; Solubility; Temperature; Triglycerides

The aim of this work is to clarify the antioxidant abilities of phenolic and enolic hydroxyl groups in curcumin. 1,7-bis(4-benzyloxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (BEC), 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-diol (OHC), 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (THC), and 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (BDC) are synthesized to determine the antioxidant activities by using antiradical assays against 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical, galvinoxyl radical, and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cation radical (ABTS*+) and by protecting DNA and erythrocyte against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) induced oxidation. The phenolic hydroxyl is the main group for curcumin to trap DPPH, galvinoxyl, and ABTS*+ radicals. The conjugative system between enolic and phenolic hydroxyl groups is beneficial for curcumin to protect erythrocytes against hemin-induced hemolysis and to protect DNA against AAPH-induced oxidation, but is not beneficial for curcumin to protect erythrocytes against AAPH-induced hemolysis. More hydroxyl groups enhance the antioxidant effectiveness of curcumin in the experimental systems employed herein. Therefore, curcumin acts as an antioxidant through the phenolic hydroxyl group.

Topics: Antioxidants; Benzhydryl Compounds; Benzothiazoles; Biphenyl Compounds; Curcumin; DNA; Free Radical Scavengers; Hemolysis; Humans; Oxidation-Reduction; Phenols; Picrates; Sulfonic Acids

alpha(S1)-Casein is one of the major protein components of the casein fraction of milk. Curcumin (diferuloyl methane), the major curcuminoid, constituting about 2-5% of turmeric (Curcuma longa ) is the active ingredient with many physiological, biochemical, and pharmacological properties. On the basis of spectroscopic measurements, it is inferred that curcumin binds to alpha(S1)-casein at pH 7.4 and 27 degrees C with two binding sites, one with high affinity [(2.01 +/- 0.6) x 10(6) M(-1)] and the other with low affinity [(6.3 +/- 0.4) x 10(4) M(-1)]. Binding of curcumin to alpha(S1)-casein is predominantly hydrophobic in nature. The anisotropy of curcumin or conformation of alpha(S1)-casein did not change on interaction. The stability of curcumin in solution at pH 7.2 was enhanced on binding with alpha(S1)-casein. The chaperone-like activity of alpha(S1)-casein gets slightly enhanced on its binding to curcumin. The ability of curcumin to protect erythrocytes against hemolysis was not affected due to curcumin- alpha(S1)-casein interaction. The two binding sites of alpha(S1)-casein for curcumin, along with enhanced solution stability on interaction, may offer an alternative approach in physiological and nutritional applications.

Topics: Animals; Binding Sites; Caseins; Cattle; Curcumin; Erythrocytes; Hemolysis; Kinetics; Molecular Conformation; Protein Binding

The antioxidant properties of curcumin have been studied by evaluating its ability to protect RBCs from AAPH (2,2'-azobis (2-amidinopropane) hydrochloride) induced oxidative damage. RBCs are susceptible to oxidative damage, resulting in peroxidation of the membrane lipids, release of hemoglobin (hemolysis), release of intracellular K(+) ions and depletion of glutathione (GSH). In this paper, lipid peroxidation, hemolysis and K(+) ion loss in RBCs were assessed respectively by formation of thiobarbituric acid reactive substances (TBARS), absorbance of hemoglobin at 532nm and flame photometry. The treatment of RBCs with curcumin showed concentration dependant decrease in level of TBARS and hemolysis. The IC(50) values for inhibition of lipid peroxidation and hemolysis were estimated to be 23.2+/-2.5 and 43+/-5microM respectively. However in contrast to the above mentioned effects, curcumin in similar concentration range, did not prevent release of intracellular K(+) ions during the process of hemolysis, rather curcumin induced its release even in the absence of hemolysis. The ability of curcumin to prevent oxidation of intracellular GSH due to hemolysis showed mixed results. At low concentrations of curcumin (<10microM) it prevented GSH depletion and at higher concentrations, the GSH levels decreased gradually. Curcumin scavenges the peroxyl radical generated from AAPH. Based on these results, it is concluded that curcumin exhibits both antioxidant/pro-oxidant activity, in a concentration dependent manner.

Topics: Amidines; Antioxidants; Biomarkers; Curcumin; Dose-Response Relationship, Drug; Erythrocyte Membrane; Erythrocytes; Glutathione; Hemoglobins; Hemolysis; Humans; Lipid Peroxidation; Oxidants; Oxidation-Reduction; Oxidative Stress; Potassium; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances

The antioxidant activities of curcumin, its natural demethoxy derivatives (demethoxycurcumin, Dmc and bisdemethoxycurcumin, Bdmc) and metabolite hydrogenated derivatives (tetrahydrocurcumin, THC; hexahydrocurcumin, HHC; octahydrocurcumin; OHC) were comparatively studied using 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical, 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) induced linoleic oxidation and AAPH induced red blood cell hemolysis assays. Hydrogenated derivatives of curcumin exhibited stronger DPPH scavenging activity compared to curcumin and a reference antioxidant, trolox. The scavenging activity significantly decreased in the order THC>HHC=OHC>trolox>curcumin>Dmc>>>Bdmc. Stronger antioxidant activities toward lipid peroxidation and red blood cell hemolysis were also demonstrated in the hydrogenated derivatives. By the model of AAPH induced linoleic oxidation, the stoichiometric number of peroxyl radical that can be trapped per molecule (n) of hydrogenated derivatives were 3.4, 3.8 and 3.1 for THC, HHC and OHC, respectively. The number (n) of curcumin and Dmc were 2.7 and 2.0, respectively, which are comparable to trolox, while it was 1.4 for Bdmc. The inhibition of AAPH induced red blood cell hemolysis significantly decreased in the order OHC>THC=HHC>trolox>curcumin=Dmc. Results in all models demonstrated the lower antioxidant activity of the demethoxy derivatives, suggesting the ortho-methoxyphenolic groups of curcumin are involved in antioxidant activities. On the other hand, hydrogenation at conjugated double bonds of the central seven carbon chain and beta diketone of curcumin to THC, HHC and OHC remarkably enhance antioxidant activity.

Topics: Amidines; Antioxidants; Biphenyl Compounds; Chromans; Curcumin; Diarylheptanoids; Erythrocyte Membrane; Free Radical Scavengers; Free Radicals; Hemolysis; Humans; Hydrogenation; In Vitro Techniques; Linoleic Acid; Lipid Peroxidation; Molecular Structure; Oxidants; Picrates; Structure-Activity Relationship; Time Factors

Curcumin (Cur), the golden yellow phenolic compound in turmeric, is well studied for its medicinal properties. In the current investigation, Cur dissolved using sodium hydroxide solution (CurNa) was tested for in vitro complement inhibitory activity and compared with rosmarinic acid (RA) and quercetin (Qur) dissolved using sodium hydroxide (RANa and QurNa, respectively) and the vaccinia virus complement control protein (VCP). The comparative study indicated that CurNa inhibited the classical complement pathway dose dependently (IC50 = 404 microM). CurNa was more active than RANa, but less active than QurNa. VCP was about 2,212, 2,786, and 4,520 times more active than QurNa, CurNa, and RANa, respectively. Further study revealed that CurNa dose dependently inhibited zymosan-induced activation of the alternate pathway of complement activation.

Topics: Analysis of Variance; Cinnamates; Complement Pathway, Alternative; Complement Pathway, Classical; Curcumin; Depsides; Hemolysis; Humans; Quercetin; Rosmarinic Acid; Viral Proteins

Hemidesmus indicus R. Br. (Asclepiadaceae) is a well known drug in Ayurveda system of medicine. In the present study, antioxidant activity of methanolic extract of H. indicus root bark was evaluated in several in vitro and ex vivo models. Further, preliminary phytochemical analysis and TLC fingerprint profile of the extract was established to characterize the extract which showed antioxidant properties. The in vitro and ex vivo antioxidant potential of root bark of H. indicus was evaluated in different systems viz. radical scavenging activity by DPPH reduction, superoxide radical scavenging activity in riboflavin/light/NBT system, nitric oxide (NO) radical scavenging activity in sodium nitroprusside/Greiss reagent system and inhibition of lipid peroxidation induced by iron-ADP-ascorbate in liver homogenate and phenylhydrazine induced haemolysis in erythrocyte membrane stabilization study. The extract was found to have different levels of antioxidant properties in the models tested. In scavenging DPPH and superoxide radicals, its activity was intense (EC50 = 18.87 and 19.9 microg/ml respectively) while in scavenging NO radical, it was moderate. It also inhibited lipid peroxidation of liver homogenate (EC50 = 43.8 microg/ml) and the haemolysis induced by phenylhydrazine (EC50 = 9.74 microg/ml) confirming the membrane stabilization activity. The free radical scavenging property may be one of the mechanisms by which this drug is effective in several free radical mediated disease conditions.

Topics: alpha-Tocopherol; Animals; Antioxidants; Apocynaceae; Ascorbic Acid; Biphenyl Compounds; Chromatography, Thin Layer; Curcumin; Erythrocyte Membrane; Free Radical Scavengers; Hemolysis; Lipid Peroxidation; Liver; Medicine, Ayurvedic; Nitric Oxide; Oxidants; Phenylhydrazines; Picrates; Plant Bark; Plant Extracts; Plant Roots; Pyrogallol; Rats; Superoxides