Photo-crosslinked, temperature-sensitive, and biodegradable pluronic hydrogels for sustained and controlled delivery of bioactive macromoelcules

Abstract

Thermally sensitive and biodegradable hydrogels based on Pluronic tri-block copolymers were prepared by a photo-polymerization method. Two terminal hydroxyl groups in Pluronic F-127 were acrylated to form a Pluronic macromer. Photo-crosslinked Pluronic hydrogels prepared by UV irradiation showed a gradually decreased swelling ratio with increasing temperature, and exhibited thermally responsive change in the swelling ratio when the temperature was cycled between 10℃ and 37℃. These Pluronic hydrogels degraded slowly due to the cleavage of ester linkage in the acrylated Pluronic terminal end. When lysozyme, a model protein drug, was loaded in the hydrogels, bi-phasic protein release profiles were attained: a burst-free and rapid controlled release profile was initially observed for a one week period and a much slower sustained release was followed thereafter. Released lysozyme from Pluronic hydrogel was almost identical to native one, indicating that UV irradiation wuth short time and low intensity did not significantly affect the conformation of lysozyme. The release rates could be controlled by varying the amount of Pluronic macromer for photo-polymerization. And, Poly(lactic-co-glycolic acid) (PLGA) microspheres were physically entrapped within the Pluronic hydrogel in order to modulate local pH environment by acidic degradation by-products of PLGA microspheres. The PLGA microspheres were slowly degraded to create an acidic micro-environment, which facilitated the cleavage of an acid-labile ester-linkage in the biodegradable Pluronic hydrogel network. The presence of PLGA microspheres accelerated the degradation of the Pluronic hydrogel and enhanced protein release rate when Bovine serum albumin(BSA), a model protein drug, was loaded in the Pluronic hydrogel.