title: Core-cross-linked polymeric micelles as paclitaxel carriers.
abstract: Cross-linkable di- and triblock copolymers of poly(epsilon-caprolactone) (PCL) and monomethoxyl poly(ethylene glycol) (MPEG) were synthesized. These amphiphilic copolymers self-assembled into nanoscale micelles capable of encapsulating hydrophobic paclitaxel in their hydrophobic cores in aqueous solutions. To further enhance their thermodynamic stability, the micelles were cross-linked by radical polymerization of the double bonds introduced into the PCL blocks. Reaction conditions were found to significantly affect both the cross-linking efficiency and the micelle size. The encapsulation of paclitaxel into the micelles was confirmed by the proton nuclear magnetic resonance (1H NMR) spectroscopy. Encouragingly, paclitaxel-loading efficiency of micelles was enhanced significantly upon micelle core-cross-linking. Both the micelle size and the drug loading efficiency increased markedly with increasing the PCL block lengths, no matter if the micelles were core-cross-linked or not. However, paclitaxel-loading did not obviously affect the micelle size or size distribution. The cross-linked micelles exhibited a significantly enhanced thermodynamic stability against dilution with aqueous solvents. The efficient cellular uptake of paclitaxel loaded in the nanomicelles was demonstrated by confocal laser scanning microscopy (CLSM) imaging. This new biodegradable nanoscale carrier system merits further investigations for parenteral drug delivery.
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-University of Marburg, Ketzerbach 63, D-35032 Marburg, Germany.
authors.forename: Xintao
authors.initials: X
authors.lastname: Shuai
authors.forename: Thomas
authors.initials: T
authors.lastname: Merdan
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Schaper
authors.forename: Fu
authors.initials: F
authors.lastname: Xi
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D016475:3T3 Cells; D000818:Animals; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects; D051379:Mice; D008823:Micelles; D008970:Molecular Weight; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D011092:Polyethylene Glycols; D017239:Paclitaxel