Self-assembled micelles based on Chondroitin sulfate/poly (d,l-lactideco-glycolide) block copolymers for doxorubicin delivery

Doxorubicin (DOX) is one of the most common chemotherapeutic agents for the treatment of various cancers, but its clinical usage is limited by dose-dependent cardiotoxicity. We have recently synthesized a series of Chondroitin sulfate/poly ( d , l -lactideco-glycolide) block copolymers (Chs- b -PLGA) with different length of hydrophobic block by an end-to-end coupling strategy. The structure of the amphiphilic block copolymers with low critical micelle concentration (∼28   mg/L) were confirmed by 1 H NMR. The copolymers could self-assemble into stable micelles in aqueous environment with homogeneous size distribution and negative zeta potential . The hemolytic study indicated their excellent blood compatibility and potential application for intravenous administration. DOX can be efficiently encapsulated by the Chs- b -PLGA micelles. The DOX-loaded micelles showed a sustained and pH dependent drug release behavior. The cytotoxicity assay showed no associated toxicity with blank micelles while concentration-related cell inhibition with DOX-loaded micelles. Moreover, fast cellular uptake of DOX-loaded micelles was observed by fluorescent microscope. In vivo pharmacokinetics study showed that the Chs- b -PLGA micelles could significantly prolong the blood circulation time of DOX. The maximum tolerated dose (MTD) of DOX-loaded micelles in Kunming mice was about 2-fold higher of the MTD of free DOX, indicating a high tolerance of the DOX-loaded micelles. In conclusion, the Chs- b -PLGA micelles would be a potentially useful drug delivery system for cancer therapy.