Zero-order release of lysozyme from poly(ethylene glycol) poly(butylene terephthalate) matrices

Protein release from a series of biodegradable poly(ether ester) multiblock copolymers, based on poly(ethylene glycol) (PEG) and poly(butylene terephthalate) (PET) was investigated. Lysozyme-containing PEG/PET films and microspheres were prepared using an emulsion technique. Proteins were effectively encapsulated and dense polymer matrices were formed. The swelling in water of PEG/PET films reached equilibrium within 3 days. The degree of swelling increased with increasing PEG content and with increasing molecular weight of the PEG segment. The release rate of lysozyme from PEG/PET films could be tailored very precisely by controlling the copolymer composition. Release rates increased with increasing PEG/PET weight ratio and increasing molecular weight of the PEG segment. For films prepared from block copolymers with PEG blocks of 4000 g/mol, first-order lysozyme release was observed. For matrices prepared from polymers with PEG segments of 1000 and 600 g/mol, the lysozyme release profile followed near zero-order kinetics. A mathematical description of the release mechanism was developed which takes into account the effect of polymer hydrolytic degradation on solute diffusion. The model was found to be consistent with the experimental observations. Finally, determination of the activity of released protein showed that lysozyme was not damaged during the formulation, storage and release periods, (C) 2000 Elsevier Science B.V. All rights reserved.