Protein release from physically crosslinked hydrogels of the PLA/PEO/PLA triblock copolymer-type

A series of PLA/PEO/PLA triblock copolymers was prepared by ring opening po lymerization of rac-lactide in the presence of various di-hydroxyl poly (et hylene glycol)s, using Call, as a biocompatible initiator. Hydrogels were p repared by a phase separation method consisting of introducing small amount s of water over solutions of the copolymers in a biocompatible organic solv ent, namely tetraglycol (poly (ethylene glycol monotetrahydrofurfuryl ether )). The resulting hydrogels appeared much more hydrophilic than the rather tough hydrogels formed by swelling of dry tablets or films processed from t he same copolymers. The phase separation-derived hydrogels were soft enough to be injected through a trochar. Two proteins, namely bovine serum albumi ne (BSA) and fibrinogen, were physically entrapped in these hydrogels by mi xing with the polymer solutions before gel formation. This procedure appear ed to be protein-respecting according to circular dichroism analysis on the released BSA. Dramatically different release profiles were obtained for th e two proteins. In the case of BSA, the release depended on the quantity of protein incorporated in the hydrogel and presented a parabolic-type profil e, in agreement with the behaviors of diffusion-controlled monolitic drug d elivery devices. In contrast, almost linear release profiles were observed in the case of fibrinogen, the hydrogels behaving like a reservoir drug del ivery system. These findings are tentatively interpreted in terms of gel-pr otein compatibility in the case of BSA and gel-protein incompatibility in t he case of fibrinogen. (C) 2001 Elsevier Science Ltd. All rights reserved.