curcumin and stearic-acid

Herein, redox responsive chitosan/stearic acid nanoparticles (CSSA NPs) (≈200 nm) are developed for dual drug delivery. These degradable nanoparticles are prepared based on disulfide (SS) crosslinking chemistry avoiding the use of any external crosslinking agent. CSSA NPs are further loaded with both DOX (hydrophilic) and curcumin (hydrophobic) drugs with ≈86 % and ≈82 % encapsulation efficiency respectively. This approach of combining anticancer therapeutics having different mode of anticancer action allows to develop systems for cancer therapy with enhanced efficacy. In vitro drug release experiments clearly exhibit the low leakage of drug under physiological conditions while ≈98 % DOX and ≈96 % curcumin is released after 136 h under GSH reducing conditions. The cytotoxicity experiments against HCT116 cells demonstrate higher cytotoxicity of dual drug loaded CSSA NPs. In vivo biodistribution experiments with c57bl/6j mice confirms the retention of CSSA NPs in the colon area up to 24 h exhibiting their potential for colorectal cancer therapy.

Topics: Animals; Chitosan; Colorectal Neoplasms; Curcumin; Disulfides; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Mice; Nanoparticles; Stearic Acids; 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

Ovarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a "core-shell" polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed.. Nuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined.. HA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic.. This special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Cell Movement; Curcumin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Hyaluronic Acid; Inhibitory Concentration 50; Mice, Inbred BALB C; Mice, Nude; Micelles; Nanoparticles; Ovarian Neoplasms; Paclitaxel; Polyethyleneimine; Polymers; Stearic Acids; Tissue Distribution; Treatment Outcome

Hybrid materials are synthesized using hydrophilic polymer and lipids which ensure their long term systemic circulation through intravenous administration and enhance loading of hydrophobic drugs. The purpose of this study is to prepare, characterize and evaluate the in vitro efficacy of curcumin loaded poly-hydroxyethyl methacrylate/stearic acid nanoparticles in MCF-7.. C-PSA-NPs, prepared using the emulsification-solvent evaporation method were characterized by dynamic laser scattering, SEM, AFM, FT-IR, X-ray diffraction, and TGA. The in vitro release behavior was observed in PBS pH7.4, the anticancer potential was analyzed by MTT assay, cell cycle and apoptosis studies were performed through flow cytometry. C-PSA-NPs drug localization and cancer cell morphological changes were analyzed in MCF-7 cell line.. C-PSA-NPs exhibited the mean particle size in the range of 184nm with no aggregation. The surface charge of the material was around -29.3mV. Thermal studies (TGA) and surface chemistry studies (FT-IR, XRD) showed the existence of drug curcumin in C-PSA-NPs. The MTT assay indicated higher anticancer properties and flow cytometry studies revealed that there were better apoptotic activity and maximum localization of C-PSA-NPs than curcumin.. Polymer lipid based drug delivery appeared as one of the advancements in drug delivery systems. Through the present study, a novel polymer lipid based nanocarrier delivery system loaded with curcumin was demonstrated as an effective and potential alternative method for tumor treatment in MCF-7 cell line.. C-PSA-NPs exhibited potent anticancer activity in MCF-7 cell line and it indicates that C-PSA-NPs are a suitable carrier for curcumin.

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle; Curcumin; Drug Delivery Systems; Humans; MCF-7 Cells; Nanoparticles; Polyhydroxyethyl Methacrylate; Spectroscopy, Fourier Transform Infrared; Stearic Acids; Thermogravimetry; X-Ray Diffraction

Curcumin (diferuloylmethane) possesses low bioavailability due to its poor solubility, permeability and rapid metabolism. Solid Lipid Nanoparticle of curcumin was prepared by high-speed homogenization technique. Stearic acid was used as a lipid, tween 80 as surfactant and various co surfactants were used for the preparation of SLN. The prepared SLN was characterized using zeta sizer, TEM analysis and the average particle size was found to be in the range of 80 nm - 200nm. The entrapment efficiency of the SLN was ~58 to 85%. The characteristic FTIR peaks suggest that the stearic acid is compatible with curcumin. MTT assay was performed on the optimized formulation and the results are indicative that curcumin SLN showed better cytotoxicity in low dose while compared to plain curcumin. The developed Cu-SLN can find its better place in the anticancer therapy.

Topics: Antineoplastic Agents; Cell Line, Tumor; Curcumin; Humans; Nanoparticles; Neuroblastoma; Particle Size; Solubility; Spectroscopy, Fourier Transform Infrared; Stearic Acids

In order to determine the efficacy of curcumin in ameliorating symptoms of neurodegeneration in the mouse model of Niemann-Pick C1, a variety of formulations and dosages of curcumin, one comparable to one previously reported as efficacious, were provided orally to Npc1(-/-)mice. Plasma levels of curcumin, survival, tests of motor performance, and memory (in some cases) were performed. We found variable, but mild, increases in survival (1.5% to 18%). The greatest increased survival occurred with the highest dose (which was unformulated) while the control for the lipidated formulation (containing phosphatidylcholine and stearic acid) had an equivalent impact and other formulations, while not significantly increased, are also not statistically different in effect from the highest dose. We conclude that curcumin is not a highly efficacious treatment for neurodegeneration in Npc1(-/-) mice. Phosphatidylcholine and stearic acid should be studied further.

Topics: Aging; Animals; Avoidance Learning; Carrier Proteins; Chromatography, High Pressure Liquid; Curcumin; Diet; Intracellular Signaling Peptides and Proteins; Lipids; Mass Spectrometry; Membrane Glycoproteins; Memory; Mice; Mice, Inbred BALB C; Mice, Knockout; Motor Activity; Nerve Degeneration; Niemann-Pick C1 Protein; Niemann-Pick Disease, Type C; Pharmaceutical Vehicles; Phosphatidylcholines; Polymerase Chain Reaction; Postural Balance; Stearic Acids; Survival

This project was undertaken with a view to optimize the treatment of inflammatory bowel disease through a novel drug delivery approach for localized treatment in the colon. Curcumin has poor aqueous solubility, poor stability in the gastrointestinal tract and poor bioavailability. The purpose of the study was to prepare and evaluate the anti-inflammatory activity of solid lipid microparticles (SLMs) of curcumin for the treatment of inflammatory bowel disease in a colitis-induced rat model by a colon-specific delivery approach.. We have developed a novel formulation approach for treating experimental colitis in the rat model. SLMs of curcumin were prepared with various lipids, such as palmitic acid, stearic acid and soya lecithin, with an optimized percentage of poloxamer 188. The SLMs of curcumin were characterized for particle size, drug content, drug entrapment, in-vitro release, surface morphology and infrared, differential scanning calorimetry and X-ray studies. The colonic delivery system of SLM formulations of curcumin were further investigated for their anti-angiogenic and anti-inflammatory activity using chick embryo and rat colitis models.. Particle size, drug content, drug entrapment and in-vitro release studies showed that formulation F4 containing one part stearic acid and 0.5% surfactant had the smallest diameter of 108 microm, 79.24% entrapment and exhibited excellent in-vitro release characteristics when compared with other formulations and pure curcumin. SLMs of curcumin (F4) proved to be a potent angio-inhibitory compound, as demonstrated by inhibition of angiogenesis in the chorioallantoic membrane assay. Rats treated with curcumin and its SLM complex showed a faster weight gain compared with dextran sulfate solution (DSS) control rats. The increase in whole colon length appeared to be significantly greater in SLM-treated rats when compared with pure curcumin and DSS control rats. An additional finding in the DSS-treated rats was chronic cell infiltration with predominance of eosinophils. Decreased mast cell numbers in the mucosa of the colon of SLMs of curcumin and pure curcumin-treated rats was observed.. The degree of colitis caused by administration of DSS was significantly attenuated by colonic delivery of SLMs of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for inflammatory bowel disease patients.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chick Embryo; Chorioallantoic Membrane; Colitis; Curcumin; Disease Models, Animal; Drug Carriers; Glycine max; Intestinal Mucosa; Lecithins; Lipids; Male; Microspheres; Neovascularization, Pathologic; Palmitic Acid; Particle Size; Rats; Rats, Sprague-Dawley; Stearic Acids