Folic acid grafted amphiphilic dextran-b-poly(ε-benzyloxycarbonyl-L-lysine) micelles for drug’s pH-responsive release

Abstract A stimulus-responsive drug delivery system holds promise for reducing adverse effects and enhancing the bioavailability of chemotherapeutic agents. In this study, amino-terminated dextran was utilized as a macromolecular initiator to prepare a range of amphiphilic dextran-b-poly(ε-benzyloxycarbonyl-l-lysine) (Dex-b-PZLL) copolymers with varying hydrophobic segment lengths via ring-opening polymerization (ROP). Folic acid (FA) was further grafted onto the dextran side chains via esterification (FA-Dex-b-PZLL), offering the potential for tumor-specific recognition. The resulting copolymers were able to self-assemble into stable spherical micelles via dialysis and efficiently encapsulate the hydrophobic drug letrozole (LTZ). A systematic assessment was conducted on the drug encapsulation efficiency/loading capacity, drug release performance in vitro, and biocompatibility of the copolymers under aqueous conditions, indicating that these properties of the FA-Dex-b-PZLL micelles mainly depended on the copolymer composition. The optimized micelles, with a balanced hydrophilic/hydrophobic ratio, achieved a drug loading capacity of approximately 8.49% and an encapsulation efficiency of about 46.39%. Moreover, LTZ/FA-Dex-b-PZLL micelles exhibited pH-responsive release, with cumulative release rates within 72 h of 20.74%, 27.14% and 62.96% in PBS at pH 7.4, 6.5 and 4.5, respectively, indicating accelerated release under acidic conditions. In addition, the micelles showed good cytocompatibility according to the CCK-8 assay.