A mechanistic study on the chemical and enzymatic degradation of PEG-Oligo(ε-caprolactone) micelles

Abstract

The chemical and enzymatic degradation of monodisperse oligo(ε-capro- lactone) (OCL) and its amphiphilic block oligomer with methoxy poly(ethylene glycol) (mPEG) were investigated in order to obtain insight into the degradation of mPEG-b-OCL micelles. Hydrolytic degradation was studied as function of pH and dielectric constant of the medium, and enzymatic degradation was investigated at different enzyme and substrate concentrations. The degradation was monitored by HPLC and MS, and the micelle destabilization with DLS. It was found that the hydrolytic degradation followed pseudo first order kinetics, and that the rate depended on the pH and dielectric constant. Degradation essentially occurred via a random scission process, and induced micelle destabilization after approximately 1.5 degradation half-lives. At physiological pH and temperature, OCLs are very stable, reflected by an estimated degradation half-life of mPEG-b-OCL micelles of several years. However, the presence of lipase resulted in an accelerated degradation with half-lives of a few days to hours. The enzymatic degradation of mPEG-b-OCL followed Michaelis-Menten kinetics. The results indicate that mPEG-b-OCL micelles are very stable in vitro, but their susceptibility to enzymes such as lipase makes these systems suitable for the hydrolysis controlled release of drugs in vivo.