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Preparation and characterization of alginate/hyaluronate hydrogel incorporating zoledronic acid-loaded chitosan microparticles for osteoarthritis therapy
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1  National University of Science and Technology "MISIS", 119049 Moscow, Russian Federation
Academic Editor: Victor Erokhin

Abstract:

Osteoarthritis features cartilage degeneration, synovial inflammation, and osteophytes, causing pain, impaired mobility, and reduced quality of life. Key causes include impaired synovial fluid biopolymer synthesis and cartilage degradation. To correct synovial fluid viscoelasticity and prevent joint inflammation, a hydrogel system of sodium alginate (SA) and sodium hyaluronate (NaHA) with zoledronic acid (ZOL) loaded chitosan microparticles (Cs-mPs) offers a promising solution.

For injectable system development, high molecular weight SA, NaHA, and Cs polymers were selected, with ZOL serving as the therapeutic agent. Viscometry determined optimal SA/NaHA concentrations and volumetric ratios prior to hydrogel formation. The hydrogel network was formed via ionic cross-linking with CaSO₄.

Subsequently, Cs-Ps were prepared via ionotropic emulsion gelation. Particle characteristics (including size, PDI, and zeta potential) were evaluated by Dynamic Light Scattering (Malvern, UK), confirming parameters essential for ionic binding with ZOL. The microparticles obtained were loaded with ZOL, with a loading capacity of 10% of mPs mass. The loaded particles were then incorporated into the hydrogel network.

At all stages of system development, cytotoxicity and cytocompatibility studies of its components were conducted using a primary human chondrocyte cell line. The obtained data indicate the absence of acute toxicity.

The results confirm the feasibility of obtaining a biocompatible SA/NaHA-based system for subsequent loading with ZOL-containing Cs-mPs and its application as a therapeutic agent for osteoarthritis treatment.

Keywords: Osteoarthritis; injectable system; biopolymer-based hydrogel; chitosan microparticles; zoledronic acid
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