Evaluation of zwitterionic polymersomes spontaneously formed by pH-sensitive and biocompatible PEG based random copolymers as drug delivery systems

Abstract

The development of stimuli-responsive biocompatible polymersomes is important for the improvement of drug delivery systems. Herein, we report the spontaneous formation of polymersomes by three random copolymers, l-cys-graft-poly[GMA-co-mPEG300], containing different ratios of l-cysteine (Cys) and methoxy poly(ethylene glycol) (mPEG) covalently linked to the polymer backbone. Cysteine was conjugated to the polymeric backbone through metal free thiol-epoxy 'click' chemistry at final step. The copolymers, without having any typical hydrophobe in the backbone, are sufficiently surface active. The self-assembly formation of the copolymers was studied in aqueous solution by steady-state fluorescence probe technique. Spontaneous polymersomes formation, without any help of stimuli and organic solvent, above a relatively low critical aggregation concentration was confirmed by dynamic light scattering and microscopic techniques. Polymersomes were shown to be able to encapsulate not only hydrophilic dye in their aqueous core but also hydrophobic guest molecules in the bilayer membrane constituted by the mPEG chains. The polymersomes are sufficiently stable under physiological condition. These nano-sized polymersomes exhibit pH-triggered release of encapsulated guest under acidic pH. All three copolymers were found to be completely cell viable and hemocompatible up to very high concentration. Their ability to cross cell membrane was demonstrated by use of a fluorescent dye-tagged polymer. Further, these copolymers did not show any denaturising effect on the secondary structure of the human serum albumin, a transport protein in the blood. Based on the results of this study it is concluded that these spontaneously formed stable and biocompatible polymersomes can have potential use as drug delivery systems.

Keywords: Biocompatible; Cell permeable; Random copolymers; Robust polymersomes; pH-responsive drug release.