DefinePK

Abstract

Objective: This study aimed to develop and evalua
te a nanoparticle-based drug delivery system for targeted release of anti-inflammatory agents in patients with osteoarthritis (OA). The objective was to enhance intra-articular drug bioavailability, prolong drug retention in joint tissues, and minimize systemic side effects often associated with oral or parenteral administration of nonsteroidal anti-inflammatory drugs (NSAIDs).
Methods: This experimental clinical study was conducted at the Tertiary Hospital of Malakand, Pakistan, from June 2023 to March 2025. Sixty adult patients diagnosed with grade II–III knee osteoarthritis (Kellgren–Lawrence scale) were enrolled. Biocompatible polymeric nanoparticles composed of chitosan and polylactic-co-glycolic acid (PLGA) were synthesized using the solvent evaporation method. Diclofenac sodium was encapsulated as the model anti-inflammatory drug. The nanoparticles were characterized for particle size, zeta potential, encapsulation efficiency, and drug release kinetics using dynamic light scattering (DLS), scanning electron microscopy (SEM), and UV–Vis spectrophotometry. Patients received a single intra-articular injection of nanoparticle formulation, and clinical parameters such as pain (VAS score), joint stiffness, and functional ability (WOMAC index) were assessed at baseline, 2 weeks, 1 month, and 3 months post-injection. Serum biomarkers of inflammation (CRP, IL-6, and TNF-α) were measured. Statistical analysis was performed using SPSS version 27, with p < 0.05 considered significant.
Results: The nanoparticles demonstrated a mean size of 185 ± 15 nm, zeta potential of +32 mV, and an encapsulation efficiency of 89%. In vitro drug release followed a biphasic pattern—an initial burst of 20% within 24 hours followed by sustained release over 21 days. Clinical follow-up revealed a significant reduction in VAS pain scores from 7.6 ± 1.2 to 3.1 ± 0.9 (p < 0.001) and improvement in WOMAC functional scores by 52% after 3 months. Serum CRP and IL-6 levels decreased by 46% and 41%, respectively. No serious local or systemic adverse effects were observed.
Conclusion: The nanoparticle-mediated intra-articular delivery of diclofenac demonstrated promising therapeutic outcomes in osteoarthritis management. The formulation enhanced local drug retention, reduced systemic toxicity, and provided prolonged anti-inflammatory efficacy. This approach could serve as a viable alternative to oral NSAID therapy, warranting further large-scale randomized clinical trials to validate its long-term safety and efficacy.