Soft biodegradable polymersomes from caprolactone-derived polymers

Polymersomes have promise for advanced theranostic delivery. We report here the design and characterization of a series of block copolymers that assemble into soft, bioresorbable, and non-toxic vesicles. The polymers are based on poly(ethylene glycol)-poly(caprolactone), but the caprolactone (CL) is copolymerized with a second monomer, 1,4,8-trioxaspiro-[4,6]-9-undecanone (TOSUO). Because TOSUO polymers have no crystalline character, copolymerizing TOSUO with CL should reduce the crystallinity of the polymersomes. After synthesizing polymers with different ratios of CL to TOSUO, we found that all copolymers assemble into both micron and nano-metric vesicles. Increasing the TOSUO content of the copolymer reduces the polymer crystalline melting temperature and the area expansion modulus of vesicle membranes. Membranes with partial crystalline structure exhibit hysteresis in the tension versus strain curve during aspiration. Vesicles are not cytotoxic and exhibit first-order release of encapsulated gemcitabine. These materials are promising for the development of deformable, biodegradable polymersomes for biomedical applications.