In vitro hydrolytic degradation of hydroxyl-functionalized poly(alpha-hydroxy acid)s

The in vitro hydrolytic degradation of hydroxyl-functionalized poly(alpha-hydroxy acid)s was investigated. Benzyl-ether-protected hydroxyl-functionalized dilactones (S)-3-benzyloxymethyl-(S)-6-methyl-1,4-dioxane-2,5-dione (1a) and (S)-3-benzyloxymethyl-1,4-dioxane-2,5-dione (1b) were copolymerized in a melt with various amounts of L-lactide using benzyl alcohol and SnOct2 as the initiator and catalyst, respectively. The benzyl groups were removed by hydrogenation to yield polyesters with hydroxyl functional groups, poly(lactic acid-co-hydroxymethyl glycolic acid) and poly(lactic acid-co-glycolic acid-co-hydroxymethyl glycolic acid) (2a and 2b). Degradation of the hydroxyl-functionalized polyesters and poly(lactic-co-glycolic acid) (50/50) was studied by incubation of pellets of these polymers in phosphate buffer (174 mM, pH 7.4) at 37 degrees C. Polymer degradation was monitored by mass-loss measurements and by gel permeation chromatography, differential scanning calorimetry, and 1H NMR analysis. The degradation times ranging from less than 1 day (for the homopolymer of 2a) to 2 months (copolymer of 25% 2a and 75% lactide) were found. The degradation rates increased with increasing hydroxyl density of the polymers, which was associated with a switch from bulk to surface erosion. NMR and thermal analysis showed that the moieties with the hydroxyl groups were preferentially removed from the degrading polymer. In conclusion, this study shows that the degradation rate of polyesters containing 2a and 2b can be tailored from a few days to 2 months, making them very suitable for biomedical and pharmaceutical applications.