Hydrolysis and Erosion Studies of Autocatalyzed Poly(ortho esters) Containing Lactoyl−Lactyl Acid Dimers

Abstract

Poly(ortho esters) based on 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane, 1,10-decanediol, and 1,10-decanediol dilactate were prepared and their hydrolysis in phosphate buffer at 37 °C and pH 7.4 was determined as a function of time. Specifically, kinetics of polymer weight loss, polymer molecular weight changes, release of lactic acid and release of propionic acid were determined. A significant decrease in molecular weight occurred within about 20 days. Weight loss and evolution of hydrolysis product occurred after an induction period that decreased with increasing content of the lactoyl-lactyl segment in the polymer. After the induction period, a concomitant rate of weight loss and release of hydrolysis products was noted. The rate increased with increasing content of the lactoyl-lactide segment. After a certain time period, size-exclusion chromatography revealed the formation of peak at an apparent molecular mass of about 550 Da. The compounds under the peak were analyzed by electrospray ionization/ mass spectrometry (ESI/MS) and found to consist of a multiplicity of lower molecular weight polymer hydrolysis fragments. On the basis of expected hydrolysis products, it was possible to assign a structure to most molecular weight peaks in the ESI/MS spectrum. The data were found to be consistent with a hydrolysis that takes place predominantly in the surface layers of the solid polymer.