Design of molecular parameters to achieve block copolymers with a powder form at dry state and a temperature-induced sol-gel transition in water without unexpected gelling prior to heating

Thermogelling block copolymers composed of polyester and polyether are faced with a dilemma of achieving powder form in order to easily handle the samples in the bulk state and avoid unexpected ahead-of-time gelling of the corresponding polymer aqueous solution below the thermogelling temperature due to the spontaneous crystallization of some polymer segments in water. In order to resolve this dilemma, we synthesized amphiphilic poly(E >-caprolactone-co-glycolide)-poly(ethylene glycol)-poly(E >-caprolactone-co-glycolide) (PCGA-PEG-PCGA) triblock copolymers with a series of ratios regarding caprolactone (CL) and glycolide (GA). The different polymer morphologies from powder to sticky paste were obatined by altering the ratios to adjust the ability of crytallization for the PCGA blocks. All of the copolymers reported in this paper were able to dissolve in water, and their aqueous solutions underwent a sol-gel transition upon heating. The polymer with an appropriate CL/GA ratio not only exhibited the powder form in the bulk state, but also achieved the sol stability in water. The triblock copolymers formed micelles in water and the micellar aggregation occurred with increasing temperature, resulting in physical gelation upon the percolation of micelles. The injectability and gellability of the copolymer-water systems were confirmed both in vitro and in vivo. Consequently, this study provides a promising injectable biomaterial, and also affords a new successful case of the molecular design of functional polymers, based upon common monomers.