Stereocomplex Micelles Based on 4-Armed Poly ( ethylene glycol ) -Polylactide Enantiomeric Copolymers for Drug Delivery

In this study, the stereocomplex micelles derived from nonlinear poly(ethylene glycol) -polylactide (PEG-PLA) enantiomeric copolymers were designed and prepared for drug delivery. First, the 4-armed PEG-PLA enantiomeric copolymers were synthesized through the ring-opening polymerization of D-lactide (DLA) and L-lactide (LLA) with 4-armed PEG as macroinitiator and stannous octoate as catalyst. 4-Armed PEG-b-PDLA micelle (PDM), 4-armed PEG-b-PLLA micelle (PLM) and 4-armed PEG-b-PDLA/4-armed PEG-b-PLLA stereocomplex micelle (SCM) were prepared through nanoprecipitation, and the morphologies, sizes and stereocomplex mechanisms of micelles were systemically characterized. It was found that the SCM showed more compact structure, smallert dynamic diameter and critical micellization concentration in contrast to PDM and PLM. Doxorubicin (DOX), a model antitumor drug,was loaded into micelles, and SCM exhibited the best drug loading capability compared with PDM and PLM. In addition, the DOX-loaded 4-armed PEG-PLA micelles, especially SCM, showed more efficient and durable capabilities for malignant cellular proliferation inhibition (e. g., HepG2 cells, a human hepatoma cell line), and exhibited less toxicities toward normal cells(e. g., L929 cells, a mouse fibroblast cell line), which revealed the great prospect of SCM for potential antitumor drug delivery.