Synthesis and characterization of pluronic-block-poly(N,N-dimethylamino-2-ethyl methacrylate) pentablock copolymers for drug/gene co-delivery systems

Abstract

We synthesized three pluronic-based cationic pentablock copolymers with different hydrophilic/lipophilic balance (HLB) values using atom transfer radical polymerization (ATRP), including PF127-block-poly(N,N-dimethylamino-2-ethyl methacrylate) (PF127-b-pDMAEMA), pluronic P123-block-poly(N,N-dimethylamino-2-ethyl methacrylate) (PP123-b-pDMAEMA), and PL121-block-poly(N,N-dimethylamino-2-ethyl methacrylate) (PL121-b-pDMAEMA). The copolymers self-assembled into core–shell structures, which could be used to co-deliver a plasmid DNA (pEGFP) and a hydrophobic drug (epirubicin, EPI). The physicochemical properties of the copolymers and drug-loaded micelles were thoroughly characterized. The micelles had a high EPI encapsulation efficiency, ∼6%, and the EPI-loaded micelles exhibited a similarly cytotoxic effect to free EPI. Among the three copolymers, the gene transfection efficiency of PL121-b-pDMAEMA was the highest, indicating that the greater the hydrophobic effect the greater cellular internalization was. The co-delivery effect of pEGFP and EPI was directly visualized using a confocal laser scanning microscope. Thus, the pluronic-b-pDMAEMA micelles are a promising co-delivery system for therapeutic pDNA and hydrophobic anticancer drugs.