Injectable Sodium Hyaluronate Hydrogels Modified by Ionic and Nonionic Polymers Loaded with Prednisolone Disodium Phosphate: Molecular Interactions and Intra-Articular Drug Delivery.

Abstract

Degenerative joint disease is a major cause of disability, and although glucocorticosteroids and hyaluronic acid are widely used to reduce inflammation and improve joint mobility, the development of effective delivery systems remains a challenge. This study describes injectable sodium hyaluronate (HA)-based hydrogels modified with synthetic polymers, including polyacrylic acid (PA), ammonium acryloyldimethyltaurate/VP copolymer (AX), a polyvinyl acetate-polyvinylpyrrolidone mixture (PVA-PVP), and polyethylene glycol 4000 (PEG), loaded with prednisolone disodium phosphate (PSP). The aim was to investigate molecular interactions between PSP and HA-based polymer networks and to determine how these interactions influence hydrogel structure, viscosity, and drug release. Viscosity was measured using a Brookfield rotational viscometer, while intermolecular interactions were analyzed by ATR-FTIR and DSC. Drug release was evaluated using a paddle-over-disc apparatus and quantified spectrophotometrically. Release kinetics were analyzed using zero-, first-, and second-order models as well as the Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin equations. PSP incorporation affected the dynamic viscosity of all formulations, and excipient type also significantly influenced hydrogel viscosity. ATR-FTIR and DSC analyses indicated hydrogen bond formation between PSP and the macromolecules of HA, PA, AX, and PEG. The PA-containing formulation formed the most extensive polymer network structure and exhibited the highest viscosity. Drug release followed mainly first-order, Higuchi, and Korsmeyer-Peppas models, while the release exponent n (0.58 ± 0.01-0.60 ± 0.01) indicated anomalous transport. These findings provide molecular insight into drug-polymer interactions in HA-based hydrogels and highlight their potential as injectable systems for intra-articular delivery of PSP.