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

Mahfoud Boustta,Michel Vert

doi:10.3390/gels6040042

Abstract

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.

Highlights

Polymeric hydrogels are 3D matrices that swell in aqueous media [1,2]
We have shown that high molar mass poly(N-acryloyl glycinamide) polymers (PNAGAs) can fulfill many of the requirements related to sustained delivery after administration by injection of a warm solution the temperature of which being tuned through polymer molar mass and concentration [14]
It has been known for several decades that free-radical polymerization of N-acryloyl glycinamide (NAGA) in water can be controlled using isopropanol as transfer agent of radicals from growing chains to monomer molecules [22]

Summary

Introduction

Polymeric hydrogels are 3D matrices that swell in aqueous media [1,2]. Hydrogels are widely implicated in countless biomedical applications [3,4]. The main domains are drug delivery and tissue engineering [5,6,7]. Water is entrapped in a 3D network of crosslinked hydrophilic macromolecules. The disappearance or the formation of inter-macromolecule bindings results in sol ↔ gel reversible phase transition. Modifications that cause such transition are referred to as stimuli [8]. PH, ionic strength, and temperature changes are stimuli exploited to modify water-polymer interactions and provoke reversible sol ↔ gel transitions

Methods

Results

Conclusion