All-trans retinoic acid release from polyion-complex micelles of methoxy poly(ethylene glycol) grafted chitosan

摘要

We synthesized a methoxy poly(ethylene glycol) grafted chitosan (ChitoPEG) copolymer to prepare a retinoic acid (RA) encapsulated polymeric micelle. The RA-encapsulated polymeric micelle of the ChitoPEG copolymer had a particle size of 100-500 nm and a spherical shape when observed by transmission electron microscopy. In a H-1-NMR study, the specific peaks of RA and chitosan as a drug-carrying inner core disappeared in deuterium oxide, and only the specific peak of methoxy poly (ethylene glycol) (MPEG) was observed, whereas specific peaks of MPEG, RA, and chitosan appeared in dimethyl sulfoxide. This indicated that the RA/ChitoPEG ion complexes were composed of a polymeric micelle with a core-shell structure and that free drug did not exist in the polymeric micelle formulations. Other evidence of drug incorporation into the polymeric micelle was witnessed in a differential scanning calorimetry analysis. The melting peaks of RA and chitosan were 182 and 220 degrees C, respectively. The melting peak of the polymeric micelle was 200 degrees C, whereas the melting peaks of the physical mixtures were those of both RA and the ChitoPEG copolymer. The lyophilized polymeric micelle was successfully reconstituted into phosphate-buffered saline without the aid of cryoprotectants. (c) 2007 Wiley Periodicals, Inc.