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 terepht halate) (PET) was investigated. Lysozyme-containing PEG/PET films and micro spheres were prepared using an emulsion technique. Proteins were effectivel y encapsulated and dense polymer matrices were formed. The swelling in wate r of PEG/PET films reached equilibrium within 3 days. The degree of swellin g increased with increasing PEG content and with increasing molecular weigh t of the PEG segment. The release rate of lysozyme from PEG/PET films could be tailored very precisely by controlling the copolymer composition. Relea se rates increased with increasing PEG/PET weight ratio and increasing mole cular weight of the PEG segment. For films prepared from block copolymers w ith PEG blocks of 4000 g/mol, first-order lysozyme release was observed. Fo r matrices prepared from polymers with PEG segments of 1000 and 600 g/mol, the lysozyme release profile followed near zero-order kinetics. A mathemati cal description of the release mechanism was developed which takes into acc ount the effect of polymer hydrolytic degradation on solute diffusion. The model was found to be consistent with the experimental observations. Finall y, determination of the activity of released protein showed that lysozyme w as not damaged during the formulation, storage and release periods, (C) 200 0 Elsevier Science B.V. All rights reserved.