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Although curcumin possesses anti-atherogenic and anti-inflammatory properties, its application is limited because of its low aqueous solubility and poor oral bioavailability. Recently, our group synthesized a novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly(ε-caprolactone) copolymer nanoparticle loading curcumin (Cur-NPs) which could improve solubility and release property of curcumin. In the present study, we further evaluated its anti-atherosclerotic effect in apolipoprotein E−/− mice. Our results demonstrated that the Cur-NPs significantly decreased atherosclerotic lesion areas and were more effective in stabilizing vulnerable plaques compared with free curcumin. The anti-atherosclerotic mechanisms of Cur-NPs include decreasing the number of introplaque microvessels, inhibiting the matrix metalloproteinase 2 and 9 activity, reducing the inflammatory response and regulating lipoprotein cholesterol metabolism more effectively compared with free curcumin. Furthermore, Cur-NPs could increase the amount of curcumin in the thoracic aorta and no significant toxicity was observed in the blood biochemical parameters in Cur-NPs-treated groups. Overall, our findings suggested that Cur-NPs could be a stabilized aqueous formulation for application with improved curcumin activity, which could be a potential treatment strategy for arteriosclerosis in the future. [ABSTRACT FROM AUTHOR]

Ketoconazole is a broad spectrum imidazole antifungal drug. For the treatment of superficial fungal infections with ketoconazole, it needs to be permeated to deep skin layers. In order to develop topical formulation of ketoconazole for improving its skin deposition and water-solubility, ketoconazole-loaded methoxy poly (ethylene glycol)-b-poly (δ-valerolactone) micelles were developed through thin-film hydration method. Particle size, drug loading capacity, infrared spectrum and X-ray diffraction of drug-loaded micelles were characterized. The optimal drug formulation was selected for skin delivery and deposition investigation performed by use of mice skin, and itsin vitrorelease and antifungal activity were also investigated. Penetration and distribution in the skin were also visualized using fluorescein-loaded micelles and fluorescence microscopy. The drug-loaded micelles were obtained with encapsulation efficiency of 86.39% and particle diameter of about 12 nm. The micelles made ketoconazole aqueous solubility increase to 86-fold higher than crude one. Ketoconazole-loaded micelles showed no skin permeation of ketoconazole, obviously enhance skin deposition and demonstrated similar antifungal activity as compared with marketed ketoconazole cream. Fluorescein-loaded micelles displayed higher skin deposition than fluorescein water solution. These results demonstrate that the MPEG-PVL micelle is a potential delivery system for ketoconazole in the field of skin delivery. [ABSTRACT FROM AUTHOR]

Purpose: To improve curcumin's pharmacokinetic, in vitro cytotoxicity and release property. Methods: A novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly (ϵ-caprolactone) copolymer was synthesized through O-alkylation, basic hydrolysis and ring-opening polymerization reaction with methoxy-poly (ethylene glycol), epichlorohydrin and ϵ-caprolactone as raw materials. Its structure was characterized by 1H-NMR and GPC. The copolymer's hemolysis and micellar encapsulation for curcumin by thin-film hydration were studied. Curcumin-loaded micelles were evaluated by use of in vitro release, FT-IR and X-ray diffraction. Curcumin-loaded micelles' in vitro cytotoxic activities against Hela and HT-29 cells were done, and its pharmacokinetic parameters were also carried out. Results: Curcumin was encapsulated into the micelles with 92.54% of entrapment efficiency and 12.84% of drug loading in amorphous forms. The dissolubility of nanoparticulate curcumin was 1.70 × 105 times higher than that of curcumin in water. The obtained copolymer showed no hemolysis. In vitro drug release study indicated that, in all cases, the kinetics was adjusted well to the Makoid-Banakar model ( = 0.9984). In addition, data were analyzed by the Korsmeyer-Peppas model, n values were 0.43, indicating that the drug release was accomplished by the combination diffusion and polymer chain relaxation. The cytotoxicity experiment indicated that the nanoparticulate curcumin kept up its potent anti-cancer activities. The pharmacokinetic results showed that the MRT0-∞, t1/2z and AUC0-∞ of Curcumin-loaded micelles were 1.64, 6.54 and 4.67 times higher than that of CUR control solution. Conclusions: The copolymeric micelles loading curcumin might act as a delivery vehicle for CUR. [ABSTRACT FROM AUTHOR]

Ketoconazole is a broad spectrum imidazole antifungal drug. For the treatment of superficial fungal infections with ketoconazole, it needs to be permeated to deep skin layers. In order to develop topical formulation of ketoconazole for improving its skin deposition and water-solubility, ketoconazole-loaded methoxy poly (ethylene glycol)-b-poly (δ-valerolactone) micelles were developed through thin-film hydration method. Particle size, drug loading capacity, infrared spectrum and X-ray diffraction of drug-loaded micelles were characterized. The optimal drug formulation was selected for skin delivery and deposition investigation performed by use of mice skin, and its in vitro release and antifungal activity were also investigated. Penetration and distribution in the skin were also visualized using fluorescein-loaded micelles and fluorescence microscopy. The drug-loaded micelles were obtained with encapsulation efficiency of 86.39% and particle diameter of about 12 nm. The micelles made ketoconazole aqueous solubility increase to 86-fold higher than crude one. Ketoconazole-loaded micelles showed no skin permeation of ketoconazole, obviously enhance skin deposition and demonstrated similar antifungal activity as compared with marketed ketoconazole cream. Fluorescein-loaded micelles displayed higher skin deposition than fluorescein water solution. These results demonstrate that the MPEG-PVL micelle is a potential delivery system for ketoconazole in the field of skin delivery.

Purpose: To improve curcumin's pharmacokinetic, in vitro cytotoxicity and release property., Methods: A novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly (ε-caprolactone) copolymer was synthesized through O-alkylation, basic hydrolysis and ring-opening polymerization reaction with methoxy-poly (ethylene glycol), epichlorohydrin and ε-caprolactone as raw materials. Its structure was characterized by (1)H-NMR and GPC. The copolymer's hemolysis and micellar encapsulation for curcumin by thin-film hydration were studied. Curcumin-loaded micelles were evaluated by use of in vitro release, FT-IR and X-ray diffraction. Curcumin-loaded micelles' in vitro cytotoxic activities against Hela and HT-29 cells were done, and its pharmacokinetic parameters were also carried out., Results: Curcumin was encapsulated into the micelles with 92.54% of entrapment efficiency and 12.84% of drug loading in amorphous forms. The dissolubility of nanoparticulate curcumin was 1.70 × 10(5) times higher than that of curcumin in water. The obtained copolymer showed no hemolysis. In vitro drug release study indicated that, in all cases, the kinetics was adjusted well to the Makoid-Banakar model ([Formula: see text] = 0.9984). In addition, data were analyzed by the Korsmeyer-Peppas model, n values were 0.43, indicating that the drug release was accomplished by the combination diffusion and polymer chain relaxation. The cytotoxicity experiment indicated that the nanoparticulate curcumin kept up its potent anti-cancer activities. The pharmacokinetic results showed that the MRT0-∞, t1/2z and AUC0-∞ of Curcumin-loaded micelles were 1.64, 6.54 and 4.67 times higher than that of CUR control solution., Conclusions: The copolymeric micelles loading curcumin might act as a delivery vehicle for CUR.