One-pot amphiphilic engineering of bioresorbable polymers for constructing colloidal vesicles and prolonging protein delivery

In this study, we sought to develop methods for amphiphilic engineering of bioresorbable polymers, sorbitan–poly(lactic acid) (sorbitan–PLA) and poly(ethylene glycol)–polylactic acid (PEG–PLA), by melt polycondensation of lactic acid in the presence of the binary initiators sorbitan and methoxy PEG in a single reactor. Briefly, oligo(lactic acid) (OLA) was first prepared by distilling water out of lactic acid under vacuum; then, sorbitan and methoxy PEG were introduced in the reactor, followed by the simultaneous polycondensation of OLA onto sorbitan and methoxy PEG, resulting in a mixture containing sorbitan–PLA/PEG–PLA copolymers. Without further purification, the recovered products were dissolved in saline buffer, mixed with squalane oil, and then homogenized to construct a stable colloidal vesicle. Then, we conducted a mechanistic study to progressively elucidate the relationship between the dispersion structure and the sustained release of a model protein bovine serum albumin. This one-pot approach has potential for applications and commercial use in the field of biodegradable controlled-release delivery systems. This study describes the production of the amphiphilic bioresorbable polymers sorbitan–PLA and PEG–PLA in a single reactor. This method aims to simplify the separation process and reduce purification costs while increasing the chemical yield. The obtained mixtures could stabilize squalene/water interfaces, resulting in a double-dispersion structure that is favorable for encapsulation in sustained delivery applications.