curcumin and tocophersolan

Using targeted liposomes to encapsulate and deliver drugs has become a hotspot in biomedical research. Folated Pluronic F87/D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) co-modified liposomes (FA-F87/TPGS-Lps) were fabricated for curcumin delivery, and intracellular targeting of liposomal curcumin was investigated.. FA-F87 was synthesized and its structural characterization was conducted through dehydration condensation. Then, cur-FA-F87/TPGS-Lps were prepared via thin film dispersion method combined with DHPM technique, and their physicochemical properties and cytotoxicity were determined. Finally, the intracellular distribution of cur-FA-F87/TPGS-Lps was investigated using MCF-7 cells.. Incorporation of TPGS in liposomes reduced their particle size, but increased the negative charge of the liposomes as well as their storage stability, and the encapsulation efficiency of curcumin was improved. While, modification of liposomes with FA increased their particle size, and had no impact on the encapsulation efficiency of curcumin in liposomes. Among all the liposomes (cur-F87-Lps, cur-FA-F87-Lps, cur-FA-F87/TPGS-Lps and cur-F87/TPGS-Lps), cur-FA-F87/TPGS-Lps showed highest cytotoxicity to MCF-7 cells. Moreover, cur-FA-F87/TPGS-Lps was found to deliver curcumin into the cytoplasm of MCF-7 cells.. Folate-Pluronic F87/TPGS co-modified liposomes provide a novel strategy for drug loading and targeted delivery.

Topics: Curcumin; Humans; Lipopolysaccharides; Liposomes; Particle Size; Poloxamer; Polyethylene Glycols

Surface functionalization enhances the properties and characteristics of polymeric nanocapsules (NCs) mainly due to the surface charge, surfactants, and polymer coating type. Curcumin (CUR) is a bioactive compound with several proven pharmacological properties and low bioavailability. This study aimed to develop anionic (poly-ɛ-caprolactone; PCL) and cationic (Eudragit. A two-level, three-factor design (polymer, Span type, and TPGS concentration) was used. The biological effects of CUR-loaded TPGS-coated cationic and anionic NCs were assessed in apomorphine-induced stereotyped behavior in rats.. The type of polymer (anionic or cationic) and Span. The CUR-loaded TPGS-coated NCs proved to be a promising brain delivery system.

Topics: Animals; Apomorphine; Behavior, Animal; Curcumin; Dopamine Agonists; Enzyme Inhibitors; Hexoses; Nanocapsules; Plants, Medicinal; Rats; Stereotyped Behavior; Treatment Outcome; Vitamin E

Topics: alpha-Tocopherol; Antineoplastic Agents; Breast Neoplasms; Caco-2 Cells; Curcumin; Doxorubicin; Female; Humans; MCF-7 Cells; Particle Size; Polyethylene Glycols; Vitamin E

Combined therapy with anti-inflammatory drugs is preferred for the topical treatment of psoriasis, but the codelivery of drugs is restricted due to the lack of a suitable delivery system. Ethosomes with excellenttransdermal propertiesare perfect as carriers for hyperplastic skin. Therefore, glycyrrhetinic acid-D-α-tocopherol acid polyethylene glycol succinate (GA-TPGS) was synthesized, which prevented the inflammation and lipid peroxidation damage, thus effectively stabilizing the psoriasis. Then GA-TPGS was surface-modified on the curcumin (Cur) loaded ethosomes to construct curcumin-loaded GA-TPGS-modified multifunctional ethosomes (Cur@GA-TPGS-ES), exerting synergistic treatment for psoriasis. Using an interleukin-6-induced cell model, we found that Cur@GA-TPGS-ES displayed desirable suppression of inflammation response and oxidative stress damage. Compared with the ethanol solution, the percutaneous penetration rates of Cur and GA in Cur@GA-TPGS-ES were superior. In vivo microdialysis revealed similar results, suggesting an increase of transcutaneous absorption in Cur@GA-TPGS-ES. Fluorescence staining revealed that the cellular uptake and skin distribution were distinctly enhanced with the delivery by Cur@GA-TPGS-ES. After topical administration to imiquimod-induced psoriatic mice, the Cur@GA-TPGS-ES group showed powerful treatment from inflammatory infiltration inhibition of Cur, glucocorticoid-like effects of GA and anti-lipid peroxidation of TPGS. Overall, GA-TPGS mediated ethosomes possess more advantageous transdermal properties and synergistic antipsoriatic efficacy.

Topics: Administration, Cutaneous; Animals; Curcumin; Drug Carriers; Glycyrrhetinic Acid; Mice; Psoriasis; Vitamin E

The oral bioavailability of curcumin is limited, attributed to its low solubility or dissolution and poor absorption. Herein, the study describes formulation of curcumin-loaded mixed micelles of Gelucire® 48/16 and TPGS for its dissolution rate enhancement. Curcumin was dispersed in these molten lipidic surfactants which was then adsorbed on carrier and formulated as pellets by extrusion spheronization. Critical micelle concentration (CMC) of binary mixture of Gelucire® 48/16 and TPGS was lower than their individual CMC demonstrating the synergistic behavior of mixture. Thermodynamic parameters like partition coefficient and Gibbs free energy of solubilization indicated that mixed micelles were more efficient than micelles of its individual components in curcumin solubilization. Dynamic light scattering (DLS) suggested slight increase in micellar size of mixed micelles than its components suggesting curcumin loading in mixed micelles. Fourier transform infrared spectroscopy (FTIR) revealed that phenolic hydroxyl group interacts with lipids which contribute to its enhanced solubility. Furthermore, the differential scanning calorimetry (DSC) and X-ray diffraction (XRD) study indicated the conversion of crystalline curcumin into amorphous form. In the pellet formulation, Gelucire® 48/16 acted as a binder and eliminated the requirement of additional binder. Microcrystalline cellulose (MCC) forms wet mass and retards the release of curcumin from pellets. Increase in concentration of water-soluble diluent increased drug release. The optimized formulation released more than 90% drug and maintains supersaturation level of curcumin for 2 h. Thus, mixed micellar system was effective delivery system for curcumin while pellet formulation is an interesting formulation strategy consisting semi-solid lipids.

Topics: Biological Availability; Curcumin; Drug Carriers; Drug Liberation; Excipients; Micelles; Polyethylene Glycols; Polymethacrylic Acids; Solubility; Vitamin E; X-Ray Diffraction

Squamous cell carcinoma treatment has limited therapeutic options and the incidence rate is increasing recently. In the present investigation, we developed poly(lactic-co-glycolic acid) (PLGA) nanopatterned films (NPFs) through poly dimethyl siloxane (PDMS) cast molding technique and explored its therapeutic efficacy in combination with curcumin and tocopherol poly (ethylene glycol) 1000 succinate (TPGS). Herein, we demonstrate the preparation and characterization of curcumin loaded tocopherol polyethylene glycol 1000 succinate stabilized poly (lactic-co-glycolic) acid nanopatterned films (CTP-NPFs). CTP-NPFs showed good in vitro cytotoxicity towards human skin cancer cell line (A431) when compared to that of unpattern films. CTP-NPFs effectively inhibited the progression of 7, 12-Dimethylbenz[a]anthracene (DMBA)/croton oil induced skin cancer in Swiss albino mice. The nanopatterned films could be used as an alternate treatment for skin cancer.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Line, Tumor; Curcumin; Drug Liberation; Humans; Mice; Nanoparticles; Particle Size; Polyethylene Glycols; Polylactic Acid-Polyglycolic Acid Copolymer; Skin Neoplasms; Vitamin E

Despite that either non-covalent or covalent attachment of hydrophilic polymers or surfactants onto nanodiamonds (NDs) could overcome the shortcomings of being a drug delivery system, it is hard to draw a definite conclusion which strategy is more effective. Hence, with the purpose of comparing the influence of different coating approach of NDs on the oral delivery efficiency of water-insoluble model drug curcumin (CUR), NDs were firstly modified with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via non-covalent or covalent conjugation method, and then loaded with CUR (CUR@NDs-COOH/TPGS or CUR@NDs-TPGS). In comparison with the core-shell-structured CUR@NDs-COOH/TPGS, CUR@NDs-TPGS were irregular in shape with dense TPGS film, and exhibited smaller size, more negatively potential, and higher drug loading efficiency. The covalent connection group also showed higher anti-cancer activity, cellular uptake, and permeability through the Caco-2 cell monolayers, as well as favorable distribution, penetration, and retention in rat intestines. The oral bioavailability study in rats demonstrated that CUR@NDs-TPGS showed significantly greater C

Topics: Administration, Oral; Animals; Biological Availability; Caco-2 Cells; Curcumin; Drug Carriers; Humans; Male; Micelles; Nanodiamonds; Particle Size; Rats; Vitamin E

Curcumin (CUR), a nontoxic natural compound with potent antitumor activity, was limited in clinical application due to its insolubility and exceedingly low bioavailability. In this study, a novel prodrug-nanoparticle (CSSV/TPGS-NPs) self-assembled by co-nanoprecipitation of CUR-s-s-vitamin E conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was prepared in attempt to solve aforementioned obstacles. CSSV/TPGS-NPs showed smaller sizes and better stability compared with that of CUR-s-s-vitamin E conjugate prodrug-nanoparticles (CSSV-NPs). Significantly, the absorption constant and effective permeability of CSSV/TPGS-NPs in different intestinal tracts increased 1.31-2.78 times and 1.81-6.95 times than that of CUR suspension, respectively. Pharmacokinetic study in Sprague-Dawley (SD) rats demonstrated that orally administered CSSV/TPGS-NPs displayed a prolonged plasma circulation with 8.06-fold increase in relative bioavailability compared to that of the CUR suspension. Altogether, conjugation of hydrophobic native CUR with vitamin E to form CSSV/TPGS-NPs is a promising technology for sustained and controlled drug delivery of CUR with improved oral bioavailability

Topics: Animals; Biological Availability; Curcumin; Drug Carriers; Nanoparticles; Polyethylene Glycols; Prodrugs; Rats; Rats, Sprague-Dawley; Vitamin E

Liver cancer is a major health problem facing mankind. Currently, the focus of research is to improve the treatment of liver cancer using a variety of treatment options such as providing chemotherapy drugs through nanocarriers.. The aim of this study was to prepare a curcumin-loaded (PLGA/TPGS) NPs delivery system by the emulsification-solvent evaporation method in order to achieve synergistic antitumor activity against liver cancer.. Curcumin-loaded (PLGA/TPGS) NPs were prepared by the emulsification and solvent evaporation method. The physical and chemical characteristics of NPs such as size, morphology, and release profiles were discussed. In vitro and in vivo studies were carried out to evaluate its anti-tumor activity in target cells.. Curcumin-loaded (PLGA/TPGS) NPs could be successfully internalized by HepG2 cells and play a synergistic role in inhibiting the growth of hepatocellular carcinoma cells. They exhibited high target organ accumulation, superior antitumor efficiency, and lower toxicity in vivo.. The present study indicates that the curcumin-loaded (PLGA/TPGS) NPs provide a promising platform for the treatment of liver cancer.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Curcumin; Dose-Response Relationship, Drug; Drug Compounding; Drug Screening Assays, Antitumor; Hep G2 Cells; Humans; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred Strains; Molecular Structure; Polylactic Acid-Polyglycolic Acid Copolymer; Structure-Activity Relationship; Vitamin E

The present investigation highlights the development of D-α-Tocopheryl polyethylene glycol 1000 succinate (Tocophersolan; TPGS) stabilized lipid nanocapsules for enhancing the oral bioavailability and permeability of curcumin (CUR). Lipid nanocapsules were optimized for different lipids, different concentrations of TPGS and different drug: lipid ratio and were further lyophilized. Subsequently, they were characterized by powder X-ray diffraction, Transmission electron microscopy and also evaluated for in vitro release study, Caco-2 cell uptake study, ex vivo intestinal permeability and in vivo pharmacokinetic performance. Optimized lipid nanocapsules exhibited desirable quality attributes (average particle size of 190 nm, polydispersity index of 0.240 and average % entrapment efficiency of 51.06 ± 7.27) employing Maisine™ 35-1 as a lipid carrier, 0.05% TPGS and CUR: lipid ratio of 5:10 and showed sustained release biphasic pattern. They showcased excellent stability in simulated gastrointestinal fluids and storage stability. The CUR nanocapsules exhibited ∼14-fold higher Caco-2 cell uptake and ∼12.8-fold increased ex vivo intestinal permeability. Also, the AUC of CUR nanocapsules in Sprague Dawley rats was increased by ∼12 folds and MRT ∼2.47-folds as compared to aqueous CUR suspension. Thus, lipid nanocapsules possessed a positive impact on improving the permeability and oral bioavailability of CUR.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Area Under Curve; Biological Availability; Caco-2 Cells; Chemistry, Pharmaceutical; Curcumin; Drug Carriers; Excipients; Humans; Intestinal Absorption; Lipids; Male; Nanocapsules; Particle Size; Permeability; Rats; Rats, Sprague-Dawley; Vitamin E

The aim of this study was to improve the solubility, oral bioavailability, and anti-gastroesophageal reflux activity of curcumin (CM) by preparing two CM-loaded, novel, binary mixed micelles (CM-M). The two CM-M were prepared by ethanol thin-film hydration method. One (CM-T) was prepared using D-alpha-tocopheryl polyethylene glycol 1000 succinate and Solutol

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Caco-2 Cells; Curcumin; Drug Carriers; Drug Compounding; Drug Evaluation, Preclinical; Drug Liberation; Gastroesophageal Reflux; Humans; Intestinal Absorption; Intestinal Mucosa; Male; Mice; Micelles; Models, Animal; Permeability; Poloxamer; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Solubility; Stearic Acids; Vitamin E

Topics: Administration, Oral; Animals; Area Under Curve; Biological Availability; Crystallography, X-Ray; Curcumin; Drug Carriers; Drug Compounding; Drug Stability; Endocytosis; Intestinal Absorption; Male; Microscopy, Electron, Transmission; Models, Statistical; Nanodiamonds; Nanomedicine; Rats, Wistar; Solubility; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Surface Properties; Technology, Pharmaceutical; Vitamin E

Topics: Antioxidants; Biological Transport; Caco-2 Cells; Curcumin; Drug Carriers; Humans; Intestinal Absorption; Nanodiamonds; Vitamin E; Vitamins

In the recent studies, it has been demonstrated that incorporation of unnatural amino acid, α,β-dehydrophenylalanine, in small peptides results in stable self-assembled nanostructures with different sizes and shapes. Here, we have replaced the natural amino acid, phenylalanine, from our earlier reported work on self-assembled peptide, Boc-Pro-Phe-Gly-OMe, with a constrained dehydro amino acid, α,β-dehydrophenylalanine, to study its influence on self-assembled nanostructures. Dehydrotripeptide, Boc-Pro-ΔPhe-Gly-OMe, self-assembled into nanostructures in aqueous solutions and formed hydrophobic matrix with improved encapsulation efficiency of hydrophobic molecules. The hydrodynamic size of peptide nanostructures from DLS study was found to be ∼257nm. The morphology and size of the loaded nanoparticles were also determined by TEM. To improve aqueous dispersibility the projected nanostructures for efficient use in drug delivery, self-assembled dehydropeptide nano carriers were further stabilized with Vitamin-E-TPGS. The final complex drug nanoparticles provided controlled drug release. These findings demonstrated that incorporation of constrained dehydro amino acids in peptides have the potential to construct stable nanostructures for development of nano materials with controlled drug release.

Topics: Curcumin; Delayed-Action Preparations; Drug Compounding; Drug Liberation; Hydrophobic and Hydrophilic Interactions; Kinetics; Nanoparticles; Oligopeptides; Ornidazole; Particle Size; Phenylalanine; Vitamin E

Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around -4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100 are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Curcumin; Drug Carriers; Female; HeLa Cells; Humans; Materials Testing; Mice; Micelles; NIH 3T3 Cells; Polyethylenes; Polypropylenes; Uterine Cervical Neoplasms; Vitamin E

Nanosuspension is one of the most promising strategies to improve the oral bioavailability of insoluble drugs. The existing techniques applied to produce nanosuspensions are classified as "bottom-up" or "top-down" methods, or a combination of both. Curcumin (CUR), a Biopharmaceutics Classification System (BCS) class IV substance, is a promising drug candidate in view of its good bioactivity, but its use is limited due to its poor solubility and permeability. In the present study, CUR nanosuspensions were developed to enhance CUR oral bioavailability using a cost-effective method different from conventional techniques.. The physicochemical properties of CUR nanosuspensions were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The crystalline state of CUR in different nanosuspensions analyzed using differential scanning calorimeter (DSC) and X-ray diffraction analysis (PXRD) confirmed its amorphous state. In vitro dissolution degree of the prepared CUR nanosuspensions using TPGS or Brij78 as stabilizer was greatly increased. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 3.18 and 3.7 times after administration of CUR/TPGS nanosuspensions or CUR/Brij78 nanosuspensions, when compared with the administration of CUR suspension.. CUR nanosuspensions produced by our cost-effective method could improve its oral bioavailability. In addition, the low-cost and time-saving method reported here is highly suitable for a fast and inexpensive preparation.

Topics: Administration, Oral; Animals; Biological Availability; Carbon Dioxide; Curcumin; Drug Stability; Male; Nanostructures; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Suspensions; Vitamin E

The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin.. The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin.. The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p < 0.01). The in situ intestinal absorption study revealed that the effective permeability (Peff) value of curcumin for SLNs was significantly improved (p < 0.01) comparing to curcumin solution.. Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.

Topics: Administration, Oral; Animals; Area Under Curve; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Availability; Curcumin; Drug Carriers; Drug Compounding; Half-Life; Intestinal Absorption; Intestine, Small; Lipids; Male; Metabolic Clearance Rate; Models, Chemical; Models, Statistical; Nanoparticles; Nanotechnology; Particle Size; Polyethylene Glycols; Rats, Wistar; Solubility; Surface-Active Agents; Technology, Pharmaceutical; Vitamin E

Nanosuspensions (NSs) were fabricated to enhance water solubility, dissolution rate, and oral adsorption of water insoluble curcumin using sonoprecipitation method. As a good stabilizer, d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) was used to improve the stability of curcumin-TPGS NSs (Cur-TPGS NSs). Ultrasonic homogenization (UH) could effectively enhance the solubility of curcumin and to produce homogeneous NSs with small particle sizes. Water solubility of curcumin was significantly improved from 0.6 μg/mL in pure water to 260 μg/mL in the mixture of curcumin and TPGS (1:10) with UH treatment. The mean particle size of Cur-TPGS NSs was decreased significantly after UH and maintained between 208 and 246 nm. Lyophilized powder of Cur-TPGS NSs was dissolved about 91.08% whereas the pristine curcumin powder was dissolved only 6.5% at pH 7.4. This study showed a great potential of Cur-TPGS NSs as a good nano-formulation of curcumin with enhanced solubility and improved oral adsorption.

Topics: alpha-Tocopherol; Chemistry, Pharmaceutical; Crystallization; Curcuma; Curcumin; Drug Stability; Nanotechnology; Particle Size; Polyethylene Glycols; Powders; Solubility; Vitamin E

The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR-MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0 nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP-TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP-TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR-MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75 mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR-MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG-PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Area Under Curve; Biological Availability; Chemistry, Pharmaceutical; Curcumin; Drug Liberation; Gastrointestinal Tract; Hydrogen-Ion Concentration; Intestinal Absorption; Kinetics; Male; Metabolic Clearance Rate; Micelles; Microscopy, Electron, Transmission; Particle Size; Polyesters; Polyethylene Glycols; Rats, Wistar; Reproducibility of Results; Vitamin E

Curcumin, a natural polyphenol compound, has been widely reported for diverse pharmacological effects and already been investigated for eye diseases. However, the water-insolubility of curcumin and the inherent penetration barriers in cornea make it difficult for curcumin to enter eye. This work aimed to develop ion-sensitive curcumin-loaded Pluronic P123 (P123)/D-a-tocopheryl polyethylene glycolsuccinate (TPGS) mixed micelle in situ gels (CUR-MM-ISGs) to prolong ocular retention time and improve cornea permeability. Central composite design-response surface methodology was applied for the optimization of curcumin-loaded P123/TPGS mixed micelles (CUR-MMs). Characterization tests showed that CUR-MMs were in spherical shape with small size and low critical micelle concentration. After dispersing the micelles in gellan gum solution (0.2%, w/w) at the ratio of 3:1 and 1:1 (v/v), respectively, CUR-MM-ISGs were formed and presented transparent appearance. Sustained release profile was obtained in vitro for both CUR-MM-ISGs (3:1 or 1:1, v/v). The irritation test proved that CUR-MM-ISGs as ophthalmic formulations were gentle and biocompatible towards ocular tissues. In addition, the ex vivo corneal penetration study indicated that the cumulative drug permeation amount of CUR-MM-ISGs (3:1, v/v) was respectively 1.16-fold and 1.32-fold higher than CUR-MM-ISGs (1:1, v/v) and curcumin solution. It can be concluded from these results that the developed ion-sensitive mixed micelle in situ gel system is a potential ophthalmic delivery carrier for curcumin as a poorly soluble drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Transport; Cornea; Curcumin; Drug Carriers; Drug Liberation; Factor Analysis, Statistical; Hydrophobic and Hydrophilic Interactions; Inflammation; Irritants; Kinetics; Male; Micelles; Particle Size; Permeability; Poloxalene; Polyethylene Glycols; Polysaccharides, Bacterial; Rabbits; Sodium Dodecyl Sulfate; Solubility; Vitamin E; Water

Self-assembled peptides and specifically small peptide based nanostructures have been the focus of research in past decade due to their potential biological applications. In this study, we prepared a protected peptide, Boc-Pro-Phe-Gly-OMe, which self-assembled in aqueous solutions leading to the formation of nanostructures and ability to act as a drug carrier. Dynamic light scattering (DLS) measurements showed nanostructures with average size of 119.6 nm containing hydrophobic core, wherein hydrophobic drugs, viz, eosin, aspirin and curcumin, were successfully encapsulated. These encapsulated nanostructures, were further stabilized with Vitamin E-TPGS. In-vitro drug release studies revealed the release of drugs in controlled fashion from the nanostructures. The results advocate the potential of the proposed peptide nanostructures as controlled drug delivery systems and could be used in other biomedical applications.

Topics: Aspirin; Cell Line; Cell Survival; Curcumin; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Liberation; Eosine Yellowish-(YS); Humans; Hydrophobic and Hydrophilic Interactions; Keratinocytes; MCF-7 Cells; Nanostructures; Oligopeptides; Particle Size; Polyethylene Glycols; Vitamin E

The biggest challenge for the treatment of multidrug resistance cancer is to deliver high concentration of anticancer drugs specifically to cancer cells for longer period of time. Poloxamers and D-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) are known inhibitors of P-glycoprotein. Mixed micelles prepared from Poloxamer 407 and TPGS may increases the therapeutic efficacy of drug by delivering high concentration of drug inside the cells and inhibition of P-gp. Curcumin (CUR) is a naturally derived novel anticancer agent but poor solubility limited its clinical use. In this study, we have developed Poloxamer 407 and TPGS mixed micelle encapsulating CUR for treatment of multidrug-resistant ovarian cancer. CUR-loaded Poloxamer 407/TPGS mixed micelles were prepared by thin film hydration method and their physicochemical properties were characterized. Cellular uptake and in vitro cytotoxicity of the CUR-loaded Poloxamer 407/TPGS mixed micelles were studied in multidrug-resistant ovarian cancer (NCI/ADR-RES) cells. The diameter of CUR-loaded Poloxamer 407/TPGS mixed micelles was about 21.4 +/- 0.3 nm and a zeta potential of -11.56 +/- 0.7 mV. The encapsulation efficiency of CUR was ranged from 95-86% with drug loading was about 1-9%. Differential scanning calorimetry and X-ray powder diffraction studies confirmed that CUR was encapsulated by the polymers. The in vitro release studies showed that mixed micelles sustained the release of CUR for more than 9 days. Results from cellular uptake studies indicated that CUR-loaded Poloxamer 407/TPGS mixed micelles had increased cellular uptake of CUR in NCI/ADR-RES cells. Cytotoxicity of CUR-loaded Poloxamer 407/TPGS mixed micelles was found to be 3 folds more than free CUR after 48 of incubations.. This study suggests that Poloxamer 407/TPGS mixed micelles might be a suitable nanocarrier for curcumin to treat multidrug resistant ovarian cancer.

Topics: Antineoplastic Agents; Cell Line, Tumor; Curcumin; Delayed-Action Preparations; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Micelles; Nanocapsules; Ovarian Neoplasms; Poloxamer; Polyethylene Glycols; Treatment Outcome; Vitamin E

Curcumin, a naturally occuring polyphenolic phytoconstituent, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). It is water insoluble under acidic or neutral conditions but dissolves in alkaline environment. In neutral or alkaline conditions, curcumin is highly unstable undergoing rapid hydrolytic degradation to feruloyl methane and ferulic acid. Thus, the use of curcumin is limited by its poor aqueous solubility in acidic or neutral conditions and instability in alkaline pH. In the present study, curcumin nanocrystals were prepared using high-pressure homogenization, to improve its solubility. Five different stabilizers [polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), sodium dodecyl sulfate (SDS), carboxymethylcellulose sodium salt] possessing different stabilization mechanism were investigated. The nanoparticles were characterized with regard to size, surface charge, shape and morphology, thermal property, and crystallinity. A short-term stability study was performed storing the differently stabilized nanoparticles at 4°C and room temperature. PVA, PVP, TPGS, and SDS successfully produced curcumin nanoparticle with the particle size in the range of 500-700 nm. PVA, PVP, and TPGS showed similar performance in preserving the curcumin nanosuspension stability. However, PVP is the most efficient polymer to stabilize curcumin nanoparticle. This study illustrates that the developed curcumin nanoparticle held great potential as a possible approach to improve the curcumin solubility then enhancing bioavailability.

Topics: Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Coumaric Acids; Curcumin; Drug Stability; Excipients; Hydrogen-Ion Concentration; Hydrolysis; Methane; Nanoparticles; Nanotechnology; Particle Size; Polyethylene Glycols; Polyvinyl Alcohol; Povidone; Pressure; Sodium Dodecyl Sulfate; Solubility; Surface Properties; Technology, Pharmaceutical; Temperature; Vitamin E

The clinical utility of curcumin (CRM) is limited due to its poor oral bioavailability. Lipid based oral formulations (LBOFs) are emerging as useful oral drug delivery systems for 'difficult to deliver' molecules like CRM. In present study, we report novel Type IV LBOF for CRM using Gelucire 44/14, Labrasol, Vit. E TPGS and PEG 400 with superior CRM loading and enhanced oral bioavailability. The optimization of LBOF for CRM loading and post dilution droplet size was carried out by design of experiments (DoE) approach with Box-Behnken design. Oral bioavailability of optimized LBOF (O-LBOF) was evaluated in male Sprague-Dawley (SD) rats at a dose of 250 mg/kg. Raw CRM (control) showed C(max) and AUC(0-∞) of 32.29 ng/ml and 38.07 ng h/ml, respectively. O-LBOF improved C(max) and AUC(0-∞) by 11.6 and 35.8 folds respectively over control.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Biological Availability; Curcumin; Drug Carriers; Excipients; Glycerides; Male; Organic Chemicals; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Solubility; Surface-Active Agents; Vitamin E

CUR is a promising drug candidate based on its good bioactivity, but use of CUR is potentially restricted because of its poor solubility and bioavailability.. The aim of this study was to prepare an aqueous formulation of curcumin nanosuspension (CUR-NS) to improve its solubility and change its in vivo behavior.. CUR-NS was prepared by high-pressure homogenization method. Drug state in CUR-NS was evaluated by powder X-ray diffraction. Pharmacokinetics and biodistribution of CUR-NS after intravenous administration in rabbits and mice were studied.. The solubility and dissolution of CUR in the form of CUR-NS were significantly higher than those of crude CUR. X-ray crystallography diffraction indicated that the crystalline state of CUR in nanosuspension was preserved. Pharmacokinetics and biodistribution results of CUR-NS after intravenous administration in rabbits and mice showed that CUR-NS presented a markedly different pharmacokinetic property as compared to the CUR solution. AUC(0-infinity) of CUR-NS (700.43 +/- 281.53 microg/mL, min) in plasma was approximately 3.8-fold greater than CUR solution (145.42 +/- 9.29 microg/mL min), and the mean residence time (194.57 +/- 32.18 versus 15.88 +/- 3.56 minutes) was 11.2-fold longer.. Nanosuspension could serve as a promising intravenous drug-delivery system for curcumin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Chemical Phenomena; Chemistry, Pharmaceutical; Curcumin; Drug Carriers; Drug Stability; Excipients; Infusions, Intravenous; Mice; Nanoparticles; Nanospheres; Particle Size; Polyethylene Glycols; Powders; Rabbits; Solubility; Suspensions; Tissue Distribution; Vitamin E