Reduction-responsive core-crosslinked micelles based on a glycol chitosan-lipoic acid conjugate for triggered release of doxorubicin

Reduction-responsive core-crosslinked micelles were developed based on a glycol chitosan-lipoic acid (GC-LA) conjugate and used for triggered release of doxorubicin (DOX). The substitution degree of GC-LA was 8.3 lipoic acid groups per 100 sugar units of glycol chitosan. GC-LA could form nanoscaled micelles in aqueous solution, wherein the critical micelle concentration (CMC) of 0.081 mg mL(-1) was determined. Furthermore GC-LA micelles can be crosslinked by a catalytic amount of dithiothreitol. The mean diameter of DOX-loaded core-crosslinked GC-LA (DOX-GC-LA/cc) micelles increased from 305 to 408 nm as the DOX-loading content increased from 6.03% to 10.74%. DOX-loaded crosslinked micelles demonstrated obvious reduction-triggered destabilization. DOX release from non-crosslinked GC-LA micelles was 87.6% for up to 96 h, whereas 25.3% of DOX release from DOX-GC-LA/cc micelles was observed in phosphate buffered saline (PBS, pH 7.4). Notably, in the presence of a 20 mM GSH-containing environment, accelerated DOX release from DOX-GC-LA/cc micelles was found. The blank micelles had low cytotoxicity in vitro, and DOX-GC-LA/cc micelles demonstrated intracellular redox-responsive characteristics in A549 cancer cells. These results suggested that GC-LA core-crosslinked micelles could be promising carriers for anticancer drug delivery.