Chitosan-poly(ε-caprolactone)-poly(ethylene glycol) graft copolymers: Synthesis, self-assembly, and drug release behavior

Biodegradable tri-component graft copolymers, chitosan-poly(epsilon-caprolactone)-poly(ethylene glycol) (CPP), were synthesized via a mild route, using sodium dodecyl sulfate-chitosan complex (SCC) as a precursor. Both PCL and PEG could be conveniently conjugated to the hydroxyl sites of chitosan without the need of tedious chemical protection/deprotection processes, thereby leaving the amino groups of chitosan intact. The self-assembly and release behavior of the copolymer micelles were investigated. Paclitaxel and rutin were used as model drugs. Spherical micelles could be formed through self-assembly of CPP in aqueous media. The micelle diameter increased with PEGylation degree and ranged from 30 to 45 nm. The incorporation of drugs into the micelles significantly raised the micelle diameter and diversified the micelle morphologies. The micelles were further subjected to glutaraldehyde treatment to prolong the release of the incorporated drugs. It was found that the crosslinking process shrunk the drug-loaded micelles. In addition, the micelles were endowed with self-luminescent properties after crosslinked with glutaraldehyde. By increasing crosslinking density, the release duration of the model drugs could be prolonged. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 96A: 116-124, 2011.