Hypoxia-sensitive micelles based on amphiphilic chitosan derivatives for drug-controlled release

Natural chitosan (CS) is composed of a larger hydrophilic skeleton with great biocompatibility. A hypoxia sensitive amphiphilic conjugate (CS-NBCF) was synthesized by conjugating CS with nitrobenzyl chloroformate (NBCF). Subsequently, nano micelles with high stability (CMC = 0.0030 mg/ml) were formed by self-assembly of the polymers in deionized water. The hypoxia-responsive function was demonstrated by examining the size variations of polymeric micelles under the hypoxia conditions. Doxorubicin (DOX) was encapsulated into the micellar core, the drug loading and encapsulation efficiency of DOX were 15.0% and 52.6%, respectively. The in vitro release experiments showed that DOX could be released rapidly in hypoxic environment, and the release amount was up to 68% in 24 h. It was found from the cytotoxicity experiment that that the toxicity of the blank micelles was low, while DOX-loaded micelles exhibited a good anti-cancer effect under hypoxic conditions, and the cell inhibition rate of MCF-7 was high up to 63%. As a result, the demonstrated properties endowed as-developed polymeric micelles with promising application as drug delivery system in tumor treatment.