Robust formation of biodegradable polymersomes by direct hydration

Herein, we report a robust way for the formation of biodegradable poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) polymersomes, via direct hydration of a highly concentrated block copolymer/oligo(ethylene glycol) solution. Polymersomes with variable membrane thickness were formed under relatively mild conditions in a short time, by changing the hydrophobic block length. Plunge freezing followed by cryo transmission electron microscopy (Cryo-TEM) was utilized to visualize the morphology of newly-formed polymersomes in their native condition. An MTT cytotoxicity study showed that the as-prepared polymersomes have good biocompatibility to hCMEC/D3 brain endothelial cells. As this method does not involve the use of small molecular organic solvent, sonication or freeze-thawing steps, it can offer the opportunity to form biodegradable polymersomes on-site. The work may facilitate the bench-to-bedside translation of biodegradable polymersomes as robust drug nanocarriers.