Methoxy poly (ethylene glycol)-b-poly (δ-valerolactone) copolymeric micelles for improved skin delivery of ketoconazole.

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.

Y-shaped Folic Acid-Conjugated PEG-PCL Copolymeric Micelles for Delivery of Curcumin.

BACKGROUND: Curcumin is a natural hydrophobic product showing anticancer activity. Many studies show its potential use in the field of cancer treatment due to its safety and efficiency. However, its application is limited due to its low water-solubility and poor selective delivery to cancer. OBJECTIVE: A Y-shaped folic acid-modified poly (ethylene glycol)-b-poly (ε-caprolactone)2 copolymer was prepared to improve curcumin solubility and realize its selective delivery to cancer. METHOD AND RESULTS: The copolymer was synthesized through selective acylation reaction of folic acid with α- monoamino poly(ethylene glycol)-b-poly(ε-caprolactone)2. Curcumin was encapsulated into the copolymeric micelles with 93.71% of encapsulation efficiency and 11.94 % of loading capacity. The results from confocal microscopy and cellular uptake tests showed that folic acid-modified copolymeric micelles could improve cellular uptake of curcumin in Hela and HepG2 cells compared with folic acid-unmodified micelles. In vitro cytotoxicity assay showed that folic acid-modified micelles improved anticancer activity against Hela and HepG2 cells in comparison to folic acidunmodified micelles. Meanwhile, both drug-loaded micelles demonstrated higher activity against Hela cell lines than HepG2. CONCLUSION: The research results suggested that the folic acid-modified Y-shaped copolymeric micelles should be used to enhance hydrophobic anticancer drugs' solubility and their specific delivery to folic acid receptors-overexpressed cancer.

Y-shaped methoxy poly (ethylene glycol)-block-poly (epsilon-caprolactone)-based micelles for skin delivery of ketoconazole: in vitro study and in vivo evaluation.

Ketoconazole is a hydrophobic broad-spectrum antifungal agent for skin infection therapy. In order to develop topical formulation of ketoconazole for improving its selective skin deposition and water-solubility, ketoconazole-loaded Y-shaped monomethoxy poly(ethylene glycol)-block-poly(ɛ-caprolactone) micelles were prepared through thin-film hydration method with high entrapment efficiency (96.1±0.76%) and small particle (about 58.66nm). The drug-loaded micelles showed comparative in vitro antimicrobial activity with KET cream. In ex in vivo skin deposition and permeation study, ketoconazole-loaded micelles provided skin accumulation higher than marketed ketoconazole cream without obvious permeation in the whole period. Fluorescence microscopy study and histopathological study demonstrated the copolymeric micelles' penetrating into skin in depth due to its capability of weakening the barrier function of stratum corneum. In vivo skin deposition parameters further confirmed high skin deposition of drug-loaded micelles (AUC(0-t)=396.16µg·h/cm2) over marketed ketoconazole cream (AUC(0-t)=250.03µg·h/cm2). Meanwhile, in vivo pharmacokinetic parameters proved that ketoconazole-loaded micelles reduced ketoconazole's distribution in blood in comparison with the cream (AUC(0-t)=93,028.00µg·h/L vs AUC(0-t)=151,714.00µg·h/L), meaning lower possibility of its systemic unwanted effects in the skin fungal infection treatment. The results suggested that the copolymeric micelles can be adopted for specific delivering ketoconazole into skin for fungal infection cure.

Y-shaped biotin-conjugated poly (ethylene glycol)-poly (epsilon-caprolactone) copolymer for the targeted delivery of curcumin.

In order to improve curcumin's low water-solubility and selective delivery to cancer, we reported ligand-mediated micelles based on a Y-shaped biotin-poly (ethylene glycol)-poly (epsilon-caprolactone)2 (biotin-PEG-PCL2) copolymer. Its structure was characterized by (1)H NMR. The blank and drug-loaded micelles obtained by way of thin-film hydration were characterized by dynamic light scattering, X-ray diffraction, infrared spectroscopy and hemolytic test. Curcumin was loaded into micelles with a high encapsulating efficiency (93.83%). Curcumin's water-solubility was enhanced 170,400 times higher than free curcumin. Biotin-PEG-PCL2 micelles showed slower drug release in vitro than H2N-PEG-PCL2 micelles. In vitro cellular uptake and cytotoxicity tests showed that higher dosage of curcumin might overcome the effect of slow release on cytotoxicities because of its higher uptake induced by biotin, resulting in higher anticancer activities against MDA-MB-436 cells. In brief, Y-shaped biotin-PEG-PCL2 is a promising delivery carrier for anticancer drug.

Poly(ethylene glycol) amphiphilic copolymer for anticancer drugs delivery.

Poly(ethylene glycol) is a water-soluble polymer. Due to its high safety and biocompatibility, it has been widely used to prepare amphiphilic copolymers for drug delivery. These copolymers can enhance water-solubility of hydrophobic drugs, improve their pharmacokinetic parameters and control their release from corresponding nanocarriers formed by its self-assembly. Anticancer drugs have some shortcomings such as lower water-solubility, bad targeting and some serious side-effects, which limit their applications and are dangerous to patients. So encapsulation of anticancer drugs into nanocarriers originated from its copolymeric derivates can improve their absorption, distribution, metabolism and excretion with better release properties and activities against cancer cells, increase their therapeutic effects, and realize their passive or active target delivery through structure modification. Recent research development of its drug delivery systems for anticancer drugs will be discussed.

Clinical Implantation with the novel D-13 prosthesis for inguinal hernioplasty: A retrospective cohort study.

INTRODUCTION: Using a mesh to repair inguinal hernias is now a standard procedure that is widely accepted as superior to primary suture repair. Although a variety of meshes are available, individual meshes may have their own unattractive features. This retrospective study examines the efficacy of our originally designed D-13 prosthesis, which is used in patients with inguinal hernias. METHODS: A total of 305 patients who underwent a herniorrhaphy between January 2009 and March 2011 were included in this study. The recurrent rate, chronic pain and feeling of a foreign body were examined at a 3-year follow-up. The D-13 prosthesis, made from clear polypropylene monofilament mesh, was originally designed by the first author of this study and constructed with the upper and lower pieces of polypropylene mesh having different shapes and sizes. Both pieces are linked together by a connector. RESULTS: The mesh is well tolerated. At a 3-year follow-up, only two patients had a foreign body sensation at the operative site, and three patients had recurrent hernias. CONCLUSION: The unique design of the D-13 prosthesis with two pieces of mesh provided encouraging long-term outcome for hernia recurrence, chronic pain and the feeling of a foreign body.