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(?‐caprolactone)₆₀₀₀‐poly(glutamic acid)₁₀₀₀ (PEG₂₀₀₀‐PCL₆₀₀₀‐PGA₁₀₀₀), was investigated. The copolymer was synthesized via ring‐opening polymerization and characterized by ¹H NMR and Fourier transform IR. The synthesized copolymer could self‐assemble into aggregates and the critical aggregation concentration was 0.23 mg 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 48 h. 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. © 2017 Society of Chemical Industry