Hyaluronic Acid-Poly(N-acryloyl glycinamide) Copolymers as Sources of Degradable Thermoresponsive Hydrogels for Therapy

Gels 2020, 6(4), 42

Mahfoud Boustta and Michel Vert



One-pot free-radical polymerization of N-acryloyl glycinamide in the presence of hyaluronic acid as transfer-termination agent led to new copolymers in high yields without any chemical activation of hyaluronic acid before. All the copolymers formed thermoresponsive hydrogels of the Upper Critical Solution Temperature-type in aqueous media. Gel properties and the temperature of the reversible gel ↔ sol transition depended on feed composition and copolymer concentration. Comparison with mixtures of hyaluronic acid-poly(N-acryloyl glycinamide) failed in showing the expected formation of graft copolymers conclusively because poly(N-acryloyl glycinamide) homopolymers are also thermoresponsive. Grafting and formation of comb-like copolymers were proved after degradation of inter-graft hyaluronic acid segments by hyaluronidase. Enzymatic degradation yielded poly(N-acryloyl glycinamide) with sugar residues end groups as shown by NMR. In agreement with the radical transfer mechanism, the molar mass of these released poly(N-acryloyl glycinamide) grafts depended on the feed composition. The higher the proportion of hyaluronic acid in the feed, the lower the molar mass of poly(N-acryloyl glycinamide) grafts was. Whether molar mass can be made low enough to allow kidney filtration remains to be proved in vivo. Last but not least, Prednisolone was used as model drug to show the ability of the new enzymatically degradable hydrogels to sustain progressive delivery for rather long periods of time in vitro.DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.