Nanostructured Cubosomal Gels for Targeted Drug Delivery in Rheumatoid Arthritis: Advances in Nanomedicine and Therapeutic Nanotechnology.

UNLABELLED: Introduction/ Objective: Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints, leading to joint destruction and systemic complications. Existing therapies, such as Disease-Modifying Antirheumatic Drugs (DMARDs) and Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), are typically associated with low efficiency, systemic side effects, and poor patient compliance. METHODS: A literature search was conducted using PubMed, Google Scholar, ScienceDirect, and Web of Science to identify relevant studies published between 2005 and 2025. The search employed the keywords "rheumatoid arthritis," "cubosomes," "cubosomal gel," "nanocarriers," and "targeted drug delivery" with Boolean operators (AND/OR). English-language studies focusing on cubosome-based drug delivery for rheumatoid arthritis were included, while non-English publications, duplicates, and unrelated studies were excluded. The selected literature was qualitatively synthesized to summarize current advances and therapeutic potential. RESULTS: Preclinical research demonstrates that cubosomal gels enhance Pharmacodynamic effects, improve drug retention in inflamed joints, and reduce systemic toxicity. Such systems show improved bioavailability and therapeutic action compared to traditional therapies. Nonetheless, issues such as scale-up manufacturing, stability, and regulatory acceptance remain. DISCUSSIONS: Cubosomal gels would be an effective platform for safer, more effective, and personalized RA therapies. New studies are advised on stimuli-responsive systems and multifunctional targeting to maximize clinical responses and translate them into patient care. CONCLUSION: Nanocarrier-based drug delivery systems offer enhanced targeted delivery and controlled release. Cubosomes, lipid-based nanostructures with bicontinuous cubic phases, effectively encapsulate both hydrophilic and hydrophobic drugs. This study demonstrates that cubosomes significantly improve topical RA treatment when incorporated into gel formulations, enhancing skin penetration, bioadhesion, and localized drug delivery. These findings have important clinical implications, suggesting cubosomes may reduce systemic side effects while maximizing therapeutic efficacy at diseased sites.