Noncytotoxic polycaprolactone-polyethyleneglycol-ε-poly(l-lysine) triblock copolymer synthesized and self-assembled as an antibacterial drug carrier

Abstract

A novel biodegradable and noncytotoxic polycaprolactone-polyethyleneglycol-ε-poly(L-lysine) (PCL-PEG-EPL) triblock copolymer was synthesized via the combination of ring-opening polymerization and facile coupling reactions. The triblock copolymer can self-assemble into vesicles in aqueous solution, and PCL forms the vesicle membrane, whereas the PEG and EPL blocks constitute the vesicle coronas. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) had proved its vesicular structure. The excellent antibacterial ability of the ε-poly(L-lysine) makes the vesicles have good antibacterial activities towards both E. coli (Gram negative) and S. aureus (Gram positive), and the minimal inhibitory concentrations (MICs) were both 62.5 μg mL⁻¹. Moreover, the special bacterial-killing mechanism of antibacterial peptides may avoid producing antibiotic-resistant bacteria. Besides, the cell viability assays showed that the triblock copolymer was noncytotoxic up to a tested concentration of 1000 μg mL⁻¹. Therefore, the copolymer vesicles have high selectivity (1000/62.5). The DOX drug loading and release profile suggested that the triblock copolymer vesicles have drug releasing ability. At the same time, in vitro enzymatic biodegradation experiments proved that the triblock copolymer vesicles could be degraded in the existence of lipid enzyme. All these results indicate that these multifunctional triblock copolymer vesicles with much lower cytotoxicity, showing antibacterial activities (without antibiotic resistance), can be a promising substitute for antibiotics. In addition, it can be used as an “armed” delivery template for anticancer drugs due to its drug delivery capacity.