Pharmacological enhancement of anti-inflammatory drug efficacy through solid lipid nanoparticles in osteoarthritis and rheumatoid arthritis: a review.

Chronic inflammatory diseases, such as rheumatoid arthritis and osteoarthritis, are sustained by dysregulated cytokine signaling, eicosanoid production, and the continuous activation of intracellular inflammatory pathways. Although nonsteroidal anti-inflammatory drugs, corticosteroids, and disease-modifying drugs are foundational treatments, their long-term use is limited due to unfavorable pharmacokinetics, lack of tissue selectivity, and systemic side effects. Solid lipid nanoparticles (SLNs) have emerged as a promising delivery system. They serve as lipid carriers, enabling better control of drug distribution while preserving pharmacodynamic effects. Preclinical studies indicate that SLN formulations can enhance the pharmacokinetics of anti-inflammatory drugs by promoting local retention, providing extended release, and increasing local drug exposure at sites of inflammation following topical, intra-articular, or systemic administration. At the molecular level, drugs delivered using SLNs consistently inhibit key inflammatory mediators, including TNF-α, IL-1β, IL-6, and PGE₂. These actions are associated with reduced activation of nuclear factor-κB and Janus kinase/signal transducer and activator of transcription pathways, as well as decreased oxidative stress and leukocyte accumulation in inflamed joints and surrounding tissues. Importantly, SLNs do not change the inherent action of the drugs they carry; instead, they enhance their pharmacological effectiveness by prolonging drug concentration at the target site and reducing exposure to non-target tissues. This fine-tuning of pharmacokinetics can lead to dose-saving strategies, which are particularly vital in the long-term management of arthritis. SLNs are an active delivery system that improves the performance of anti-inflammatory drugs by modulating controlled exposure and altering molecular pathways. However, further prolonged dosing studies and clinical trials are necessary to fully establish their clinical utility.