Synthesis of a chemically-crosslinked thermo-sensitive hydrogel film and in situ encapsulation of model protein drugs

An intelligent and biodegradable hydrogel film was prepared via polymerization of a well-designed macromer, and in situ encapsulation of model protein drugs in the hydrogel was performed in this paper. Hydrogels were prepared by polymerization of a synthetic macromer, in which the central part is a temperature-sensitive triblock copolymer composed of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), the extension along each end is biodegradable oligo (epsilon-caprolactone) (oligoCL) terminated with an acrylate group. The biodegradability of the resultant hydrogels was confirmed. The swelling/deswelling experiments revealed the negative and reversible temperature-sensitivity of the hydrogels. The volume phase transition temperature is between the refrigerator temperature and human body temperature. Four model protein drugs (insulin, lysozyme, SOD and BSA) were encapsulated into the hydrogel via in situ polymerization of macromer aqueous solutions mixed with proteins. Proteins were found to be controlled released and the release rate was strikingly influenced by temperature. The in vitro release profiles of proteins of different molecular weights (MW) were measured. The half release time is found to be positively related to the molecular weight of examined model proteins. The novel chemically crosslinked hydrogels might be prospective as controlled-release carriers of biomacromolecular drugs. (C) 2005 Elsevier B.V. All rights reserved.