Relationship among drug delivery behavior, degradation behavior and morphology of copolylactones derived from glycolide, L-lactide and ε-caprolactone

A series of copolylactones was synthesized by ring-opening copolymerization of glycolide, L-lactide and epsilon-caprolactone, using stannous octoate as catalyst. The in vitro degradation behaviors of them were studied and data demonstrated different degradation rates which mainly depended on the compositions. Investigation of the 5-fluorouracil (5-Fu) release from these copolylactones revealed that the composition, degradation rate and the morphology of the polymeric matrix played an important role on the drug release kinetics. A sustained 5-Fu release without initial time lag was obtained from random poly(lactide-co-glycolide-co-caprolactone) (r-PGLC) drug carrier, and it differed from the cases of polylactide (PLA) or random poly(lactide-co-glycolide) (PLGA), which usually showed an initial time lag or biphasic drug release behavior. It was due to the low, glass transition temperature (T-g) of the r-PGLC and the drug would diffuse faster in rubbery state under the experimental temperature. Furthermore, a significant change in the drug release behavior of r-PGLC was observed when the temperatures were changed around the T-g of the drug carrier, which implied that the drug release behavior could be regulated by adjusting the morphology of the drug carrier. Copyright (C) 2002 John Wiley Sons, Ltd.