Thermo-sensitive injectable hydrogel based on the physical mixing of hyaluronic acid and Pluronic F-127 for sustained NSAID delivery

Abstract

The aim of this research is the development of a new type of intra-articularly injectable thermo-sensitive hydrogels for the long-term delivery of Piroxicam (PX). The thermo-sensitive hydrogel was prepared by the simple physical mixing of HA and Pluronic F-127 (HP) in aqueous solution. The addition of high-molecular-weight HA not only enhanced the mechanical strength of the hydrogel but also elicited a sustained drug release. This result could be attributed to the high-molecular-weight HA-assisted inter-micellar packing in the hydrogel inner structure. The critical gelation temperature value of HP hydrogel was considerably lower than native Pluronic F-127. To evaluate the bioavailability, pharmacokinetic parameters were analyzed after articular-cavity injection of the HP hydrogel in beagle dogs. The HP hydrogel exhibits both sustained drug release behavior and superior bioavailability in physiological conditions. Thus, we believe that the NSAID PX-loaded HP hydrogel could be a promising hydrogel-based drug delivery platform for the treatment of arthritis.

Keywords: Arthritis; Hyaluronic acid (HA); NSAID; Pluronic F-127; Thermo-sensitive hydrogel.