ADVANCED LIPOSOMAL CO-DELIVERY STRATEGIES FOR SYNERGISTIC ANTI-INFLAMMATORY THERAPY

Inflammation is a complex physiological response associated with the progression of numerous acute and chronic diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, pulmonary disorders, neurodegenerative conditions, and cardiovascular diseases. Although conventional anti-inflammatory therapies such as nonsteroidal anti-inflammatory drugs (NSAIDs): corticosteroids, and immunosuppressive agents are widely used, their long-term administration is often limited by poor bioavailability, rapid metabolism, systemic toxicity, non-specific tissue distribution, and severe adverse effects. To overcome these limitations, liposomal nanocarrier systems have emerged as promising drug delivery platforms due to their biocompatibility, biodegradability, controlled release behavior, and targeting potential. Among these systems, dual drug-loaded liposomes have gained considerable attentionfor their ability to simultaneously deliver two therapeutic agents with complementary mechanisms of action, thereby enhancing synergistic anti-inflammatory efficacy while reducing toxicity and dosing frequency. This review highlights recent advances in dual drug-loaded liposomal systems developed for synergistic anti-inflammatory therapy. It discusses the structural organization, composition, classification, and formulation strategies of liposomes, including thin-film hydration, reverse-phase evaporation, ethanol injection, and active loading methods. Important physicochemical characterization parameters such as particle size, zeta potential, entrapment efficiency, drug release behavior, and stability are also summarized. Particular emphasis is placed on the co-delivery of synthetic anti-inflammatory drugs with natural bioactive compounds, antioxidants, immunomodulators, and nucleic acid therapeutics for simultaneous modulation of inflammatory pathways including NF-κB, MAPK, COX-2, cytokine signaling, and oxidative stress-mediated mechanisms. Furthermore, recent in vitro and in vivo studies demonstrating enhanced therapeutic efficacy, controlled drug release, reduced inflammatory cytokine production, and targeted accumulation at inflamed tissues are critically discussed. The review also addresses current challenges associated with large-scale manufacturing, formulation stability, regulatory approval, and clinical translation. Overall, dual drug-loaded liposomal systems represent highly promising nanotherapeutic platforms for the development of safer, more effective, and targeted anti-inflammatory therapies in the future.