Semi-interpenetrating network of poly(ethylene glycol) and poly(D, L-lactide) for the controlled delivery of protein drugs

Abstract

We have prepared a semi-interpenetrating network (IPN) of poly(ethylene glycol) dimethacrylate (PEGDMA) with entrapped poly(D, L-lactide) (PLA) using photochemical techniques. These IPNs were developed for the controlled delivery of protein drugs such as growth factors. The PEG component draws water into the network, forming a hydrogel within the PLA matrix, controlling and facilitating release of the protein drug, while the PLA component both strengthens the PEG hydrogel and enhances the degradation and elimination of the network after the protein drug is released. The rate and extent of swelling and the resultant protein release kinetics could be controlled by varying the PEG/PLA ratio and total PLA content. These IPNs were prepared using a biocompatible benzyl benzoate/benzyl alcohol solvent system that yields a uniform, fine dispersion of the protein throughout the PEG/PLA IPN matrix. IPNs composed of high molecular mass PLA and lower PEG/PLA ratios exhibited lower equilibrium swelling ratios. The release of bovine serum albumin (BSA), a model protein, from these IPNs was characterized by a large initial burst, regardless of the PEG/PLA ratio, due to the entrapment of residual solvent within the network. Microparticles of the PEG/PLA IPNs were also prepared using a modified Prolease® strategy. Residual solvent removal was significantly enhanced using this process. The microparticles also exhibited a significant reduction in the initial burst release of protein. Mixtures of different compositions of PEG/PLA microparticles should be useful for the delivery of a variety of protein drugs with different release kinetics from any tissue-engineering matrix.