pH-responsive poly(ethylene glycol)-poly(ε-caprolactone)-poly(glutamic acid) polymersome as an efficient doxorubicin carrier for cancer therapy

The synthesis, characterization and potential application in the doxorubicin (Dox) delivery system of a biodegradable polypeptide-based block copolymer, poly(ethylene glycol)(2000)-poly(epsilon-caprolactone)(6000)-poly(glutamic acid)(1000) (PEG(2000)-PCL6000-PGA(1000)), was investigated. The copolymer was synthesized via ring-opening polymerization and characterized by H-1 NMR and Fourier transform IR. The synthesized copolymer could self-assemble into aggregates and the critical aggregation concentration was 0.23mg mL(-1). Transmission electron microscopy indicated that spherical polymersomes formed with a desirable size about 180 nm. Therefore Dox was encapsulated into these polymersomes, and then we investigated its applications in a drug delivery system. These Dox-loaded polymersomes (PolyDox) were characterized by dynamic light scattering, zeta potential and pH responsiveness measurements. In vitro drug release indicated that the release rate of drug from PolyDox was pH-responsive and significantly decreased. The drug pharmacokinetic parameters were improved in comparison to the group treated with free Dox, which proved the prolonged Dox release from PolyDox. A WST-1 assay indicated a low toxicity and good compatibility of copolymer to cells within 48h. The results also showed that PolyDox appeared to induce a higher anti-tumor effect. Cell uptake results indicated that PolyDox displayed higher cellular uptake in A549 cells. Endocytosis inhibition results demonstrated that the internalization of PolyDox was mostly mediated by the fluid-phase endocytosis pathway. (C) 2017 Society of Chemical Industry