Core-shell-corona chitosan-based micelles for tumor intracellular pH-triggered drug delivery: Improving performance by grafting polycation

Core-shell-corona chitosan-based micelles were designed for the tumor intracellular pH-triggered doxorubicin (DOX) delivery, via a facile in-situ micellization in an aqueous solution of DOX and polyethylene glycol (PEG) and poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) dual-modified chitosan (PEG-g-CS-g-PDPA). The effect of the PDPA modification on the diameter, drug loading-capacity (DLC) and pH-triggered drug release was investigated for the three different polymerization degrees of PDPA (25, 32, and 42) with a similar modification degree of ~22%. The optimized ones, the core-shell-corona DOX/PEG-g-CS-g-PDPA 32 micelles possessed a mean hydrodynamic diameter (D h ) of 211 nm and DLC of 54%, showing an excellent pH-triggered drug release with negligible premature drug leakage in 60 h. Such results indicated that grafting polycation could efficiently improve the performance of the chitosan-based drug delivery system (DDS) for tumor chemotherapy.