A robust pH-sensitive drug carrier: Aqueous micelles mineralized by calcium phosphate based on chitosan

This study developed an exciting alternative to the polymeric delivery system in cancer therapy. In this study, novel organic–inorganic hybrid polymeric micelles based on chitosan were synthesized and found to be robust nanocarriers for intracellular controlled release drug delivery. The polymeric micelles of carboxymethyl chitosan-grafted-p(ethylene glycol)-dodecylamine (CMC-g-PEG-DDA) were readily mineralized in the presence of calcium chloride (CaCl2) and disodium hydrogen phosphate (Na2HPO4). Mineralization reduced polymeric micelles’ size from 239 nm to 138 nm and formed a multi-core structure. The mineralized polymeric micelles (MPM) exhibited enhanced serum stability. The DOX release from the DOX-loaded mineralized polymeric micelles (MPM@DOX) at physiological pH was efficiently inhibited, At an endosomal pH (pH 5.0), DOX release was facilitated due to rapid dissolution of the calcium phosphate (CaP). These results indicate that mineralized polymeric micelles are potentially as robust carriers that can release DOX at specific sites under mild acidic conditions, such as in an extracellular matrix of tumor tissue and intracellular cell compartments.