Preparation and characterization of long-circulating PELMD/mPEG–PLGA-mixed micelles for 10-hydroxycamptothecin

A novel long-circulating nano-delivery system was constructed using block copolymers of poly monomethoxy-(ethylene glycol)-poly(d,l-lactic-co-glycolic acid)-poly(3(S)-methyl-morpholine-2,5-dione) (PELMD) and poly-monomethoxy (ethylene glycol)–poly-(d,l-lactic-co-glycolic acid) (mPEG–PLGA). The two copolymers possessed satisfactory critical micelle concentration and hemolytic effect. Antitumor compound 10-hydroxycamptothecin (HCPT) was loaded to the mixed micelles to further characterize in vitro and in vivo properties. HCPT-mixed micelles were measured 165–205 nm in particle size, with spherical core–shell structure and uniform-size distribution. The zeta potentials of the mixed micelles ranged 15–20 mV, attributed to the polydesipeptide. Stability of the mixed micelles was improved without complex synthesis. Drug release from the mixed micelles was pH-dependent, which was beneficial for improving specific drug targeting to tumor tissues. HCPT-mixed micelles demonstrated prolonged retention and tissue targeting in animal models. Mean residence time (MRT_0→∞) of HCPT-mixed micelles was significantly longer than that of HCPT injection, and biodistribution of the mixed micelles showed specific drug disposition in liver and lungs. The results indicated that PELMD/mPEG–PLGA-mixed micelles could become a potential drug delivery system for anticancer drugs to improve therapeutic efficacy and minimize adverse effects.