A glucosyl triblock copolymer: synthesis and its injectable thermo- and pH-responsive behaviours

A new glucosyl triblock copolymer, poly(acryloyl glucofuranose)-block-poly(N-isopropyl acrylamide)-block-poly(acrylic acid) (PAG-b-PNIPAM-b-PAA, i.e., PGNA), was first synthesized from 3-O-acryloyl-1,2; 5,6-di-O-isopropylidene-alpha-D-(-)-glucofuranose (ADIPG), tert-butyl acrylate (tBA) and N-isopropyl acrylamide (NIPAM) in the presence of the initiator 2,2-azoisobutyronitrile (AIBN) by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization. In this RAFT process, 2,2'-thiocarbonylbis(sulfanediyl)bis(2-methylpropanoic acid) (CMP) was synthesized and used as a chain transfer agent. PGNA and the reaction intermediates were characterized by FT-IR, HNMR and GPC. When heated, the aqueous PGNA copolymer solution exhibits good sol-gel phase transition behaviours. Meanwhile, the formed hydrogels are also sensitive to the pH. When the copolymer solution is injected into a living Sprague Dawley (SD) rat, an in situ gel is formed within 3 minutes. By using acetylsalicylic acid (aspirin) as a model, drug release tests show that the maximum releasing value is approximately 76% under physiological conditions (pH 7.4, 37 degrees C). The synthesized triblock copolymer shows no apparent cytotoxicity towards L929 fibroblast cells according to an in vitro cytotoxicity test (MTT assay).