EMERGING NANOGEL DRUG DELIVERY PLATFORMS FOR IMPROVED THERAPEUTIC PERFORMANCE OF METHOTREXATE

Methotrexate (MTX) remains a cornerstone antimetabolite in the management of malignancies and autoimmune disorders, including rheumatoid arthritis and psoriasis. However, its conventional administration is hindered by significant limitations such as poor and variable bioavailability, rapid systemic clearance, dose-limiting toxicity, and lack of precise site-specific targeting. These challenges often compromise therapeutic outcomes and increase the risk of severe adverse effects, thereby necessitating innovative and more efficient drug delivery strategies. Nanogel-based drug delivery systems have recently gained considerable attention as next- generation nanocarriers designed to address these shortcomings. Nanogels are three-dimensional, nanoscale, cross-linked polymeric networks characterized by high water content, excellent biocompatibility, and structural versatility. Their ability to encapsulate therapeutic agents and respond to physiological stimuli such as pH, temperature, and enzymatic activity makes them highly efficient for controlled and targeted drug delivery. The incorporation of MTX into nanogels offers multiple therapeutic advantages, including enhanced drug stability, prolonged circulation time, improved bioavailability, and selective accumulation at diseased tissues via passive and ligand-mediated active targeting mechanisms. Furthermore, sustained and controlled drug release significantly reduces systemic toxicity and improves overall treatment efficacy and patient compliance. Recent advances in nanogel engineering, including smart and stimuli-responsive systems, have demonstrated promising results in preclinical studies, indicating superior therapeutic performance compared to conventional formulations. Nonetheless, challenges such as scalability, reproducibility, long-term safety, and regulatory approval must be addressed. Overall, nanogel platforms represent a transformative and highly promising strategy for optimizing MTX therapy in modern precision medicine.