Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems

Stimuli-responsive polymersomes have emerged as smart drug delivery systems for programmed release of highly cytotoxic anticancer agents such as doxorubicin hydrochloride (Dox center dot HCl). Recently, a biodegradable redox-responsive triblock copolymer (mPEG-PDH-mPEG) was synthesized with a central hydrophobic block containing disulfide linkages and two hydrophilic segments of poly(ethylene glycol) methyl ether. Taking advantage of the self-assembly of this amphiphilic copolymer in aqueous solution, in the present investigation we introduce a solvent-exchange method that simultaneously achieves polymersome formation and drug loading in phosphate buffer saline (10 mM, pH 7.4). Blank and drug-loaded polymersomes (5 and 10 wt.% feeding ratios) were prepared and characterized for morphology, particle size, surface charge, encapsulation efficiency and drug release behavior. Spherical vesicles of uniform size (120-190 nm) and negative zeta potentials were obtained. Dox center dot HCl was encapsulated into polymersomes with a remarkably high efficiency (up to 98 wt.%). In vitro drug release studies demonstrated a prolonged and diffusion-driven release at physiological conditions (similar to 34% after 48 h). Cleavage of the disulfide bonds in the presence of 50 mM glutathione (GSH) enhanced drug release (similar to 77%) due to the contribution of the erosion mechanism. Therefore, the designed polymersomes are promising candidates for selective drug release in the reductive environment of cancer cells.

Automated summary

In this study, we successfully synthesized stimuli-responsive polymersomes that can respond to the tumor cell environment, and demonstrated their efficient encapsulation and release of the highly cytotoxic anticancer drug doxorubicin hydrochloride (Dox center dot HCl). The polymersomes were formed under physiological conditions using a solvent-exchange method, and showed stable morphology and size. In vitro release studies revealed a delayed release of the drug from the polymersomes, and enhanced drug release through cleavage of the disulfide bonds in the reductive environment.