An injectable biodegradable temperature-responsive gel with an adjustable persistence window

Abstract ε-Caprolactone (CL) and 3-benzyloxymethyl-6-methyl-1,4-dioxane-2,5-dion (fLA), with a benzyloxymethyl group at the 3-position of the lactide, were randomly copolymerized. The methoxy polyethylene glycol (MPEG)- b -[poly(ε-caprolactone)- ran -poly(3-benzyloxymethyl lactide) (PCL- ran -PfLA)] diblock copolymers were designed such that the PfLA content (0–15 mol%) in the PCL segment was varied. The MPEG- b -(PCL- ran -PfLA) diblock copolymers were derivatized by introducing a pendant benzyl group (MCx Ly -OBn), hydroxyl group (MCx Ly -OH), or carboxylic acid group (MCx Ly -COOH) at the PfLA segment. The derivatized MPEG- b -(PCL- ran -PfLA) diblock copolymer solutions exhibited sol-to-gel phase transitions upon a temperature increase. The sol-to-gel phase transition depended on both the type of functional pendant group on the PfLA and the PfLA content in the PCL segment. MCx Ly -COOH diblock copolymer solutions formed gels immediately after injection into Fischer rats. The gels gradually degraded over a period of 0–6 weeks after the initial injection, and the rate of degradation increased for higher concentrations of PfLA. Immunohistochemical characterization showed that the in vivo MPEG- b -(PCL- ran -PfLA) diblock copolymer gels provoked only a modest inflammatory response. These results show that the MPEG- b -(PCL- ran -PfLA) diblock copolymer gel described here may serve as a minimally invasive therapeutic, in situ-forming gel system with an adjustable temperature-responsive and in vivo biodegradable window.