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 polymerization of rac-lactide in the presence of various di-hydroxyl poly (ethylene glycol)s, using CaH2 as a biocompatible initiator. Hydrogels were prepared by a phase separation method consisting of introducing small amounts of water over solutions of the copolymers in a biocompatible organic solvent, 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 the same copolymers. The phase separation-derived hydrogels were soft enough to be injected through a trochar. Two proteins, namely bovine serum albumine (BSA) and fibrinogen, were physically entrapped in these hydrogels by mixing with the polymer solutions before gel formation. This procedure appeared to be protein-respecting according to circular dichroism analysis on the released BSA. Dramatically different release profiles were obtained for the two proteins. In the case of BSA, the release depended on the quantity of protein incorporated in the hydrogel and presented a parabolic-type profile, in agreement with the behaviors of diffusion-controlled monolitic drug delivery devices. In contrast, almost linear release profiles were observed in the case of fibrinogen, the hydrogels behaving like a reservoir drug delivery system. These findings are tentatively interpreted in terms of gel-protein compatibility in the case of BSA and gel-protein incompatibility in the case of fibrinogen.