Development of injectable ibuprofen and resveratrol co-loaded mesoporous silica nanoparticle-based hydrogels for sustained delivery in osteoarthritis management.

This study reports the synthesis of mesoporous silica nanoparticles (MSNs), MCM‑41 (M41) and SBA‑15 (S15), individually loaded with ibuprofen (M41IF, S15IF) and resveratrol (M41RS, S15RS). These drug‑loaded MSNs were formulated into thermoresponsive injectable hydrogels (M41IFRSG and S15IFRSG) for intra‑articular delivery to achieve localised therapy for osteoarthritis (OA). The synthesised MSNs exhibited high surface areas (1008 m²/g for M41 and 706 m²/g for S15), large pore volumes (0.303 cc/g and 0.790 cc/g), and efficient drug loading (18%-53%). In vitro drug release studies revealed rapid ibuprofen release and sustained resveratrol release (41%-43% over 48 h), supporting prolonged anti‑inflammatory and antioxidative activity. The sterility test confirmed that no visible microbial growth occurred on tryptic soy broth (TSB) or fluid thioglycollate medium (FTG) plates for any formulation during 7‑day incubation at 37 °C, ensuring microbiological safety. In a papain‑induced OA rat model, both formulations preserved bone composition and joint architecture, as verified by radiographic and micro‑CT analyses showing wider joint space and fewer osteophytes. Interestingly, the drugs loaded into the MCM-41 MSNs-based gel exhibited superior therapeutic efficacy compared to those loaded into the SBA-15 MSNs-based gel. Histological evaluation revealed restored cartilage tissue, minimal fibrous proliferation, and reduced inflammatory infiltration. Biochemical assays showed a 50-60% reduction in TNF‑α, IL‑1β, and IL‑6 levels, restoration of IL‑10, and a 40-55% decrease in malondialdehyde and nitrite content. Myeloperoxidase activity also declined markedly. Overall, M41IFRSG displayed greater therapeutic potential than S15IFRSG, effectively mitigating inflammation, oxidative stress, and joint degeneration associated with OA.