ADVANCED NANOTHERAPEUTICS IN MULTIPLE SCLEROSIS TREATMENT: FROM BLOOD-BRAIN BARRIER CROSSING TO REMYELINATION ENHANCEMENT

Multiple sclerosis (MS) is a debilitating autoimmune demyelinating disorder characterised by chronic inflammation, progressive neurodegeneration, and failed remyelination. Current disease-modifying therapies remain limited by poor blood-brain barrier (BBB) penetration, systemic toxicity, and inadequate targeting of pathological processes. This review comprehensively analyses the role of nanotechnology in overcoming these therapeutic hurdles, examining cutting-edge platforms that address BBB crossing, immunomodulation, and remyelination enhancement in MS treatment. Three primary nanotechnology platforms demonstrate exceptional therapeutic potential: Gold nanocrystals (CNM-Au8) showing remarkable remyelination activity through energy metabolism enhancement, currently in Phase 2 clinical trials with demonstrated oral bioavailability and BBB penetration; PLGA nanoparticles loaded with myelin antigens inducing robust antigen-specific immune tolerance via tolerogenic immune-modifying mechanisms, preventing disease progression in preclinical models; and Extracellular vesicles providing natural BBB crossing capability with superior immunomodulatory and remyelination-promoting effects through microRNA and growth factor delivery. Additional promising platforms include mannosylated liposomes for targeted antigen delivery, solid lipid nanoparticles for enhanced brain bioavailability, and phosphorus-based dendrimers for precision immunomodulation. These approaches demonstrate significant improvements in motor function, reduced neuroinflammation, enhanced myelin repair, and induction of long-lasting immune tolerance. Despite remarkable preclinical success and early clinical validation, challenges in manufacturing scalability, regulatory translation, and long-term safety profiles remain. Future efforts must focus on clinical translation through optimised targeting designs, standardisedcharacterisation protocols, and comprehensive toxicity studies to realise the transformative potential of precision nanomedicine in MS therapy.