Chemo-enzymatic synthesis and sustained release of optically active polymeric prodrugs of chlorphenesin

Optically active polymeric prodrugs containing saccharides were prepared via a facile procedure combining enzymatic resolution with chemical polymerization. Polymerizable optically active chlorphenesin derivatives were obtained in excellent optically purity (ee > 99.9%) and high yield (∼50%) in short time (∼4 h) by lipase-catalyzed resolution after optimization of reaction conditions. Then, polymerizable optically active monomer was copolymerized with different polymerizable glycolipids using free radical polymerization method. The obtained optically active polymeric prodrugs bearing (R)-chlorphenesin residue were characterized by IR, NMR and GPC. In vitro released studies showed that the cumulative released optically pure chlorphenesin (ee = 88–92%) from the polymeric prodrug (VADG) was from 19.3% to 34.3% in pH 7.4, pH 5.4 and pH 1.2 after 7 days. The cumulative liberation rate of optically active polymeric prodrugs (ee = ∼88%) with different glycolipids was from 26.4% to 38.5% in pH 1.2.