Targeted Drug Delivery in Animal Models of Demyelination: The Role of Plant-Based Nanoparticles with a Focus on Multiple Sclerosis.

Demyelinating diseases disrupt neural signaling through immune-mediated myelin damage, leading to sensory, motor, and cognitive deficits, particularly in multiple sclerosis (MS). The blood-brain barrier (BBB) limits drug delivery to the central nervous system (CNS), restricting therapies like fingolimod, which manage inflammation but do not support remyelination. Plant-based nanoparticles (NPs) with phytochemicals offer biocompatible, anti-inflammatory, antioxidant, and neuroprotective advantages, presenting alternatives for treatment. This review explores the therapeutic potential of plant-based NPs in MS using demyelination models such as experimental autoimmune encephalomyelitis (EAE) and cuprizone. Preclinical studies suggest that plant-based NPs alleviate neuroinflammation and facilitate remyelination by crossing the BBB through receptor-mediated transcytosis. Nevertheless, challenges emerge from variability in phytochemical compositions, distinct gaps contingent upon the models employed, an absence of data from all demyelination models, and inadequate behavioral assessments, all of which impede progress. Plant-based NPs demonstrate promise in addressing issues related to the BBB and MS pathology. To advance this, high-throughput screening of phytochemicals, standardized synthesis processes, and thorough behavioral studies in chronic models are crucial. Furthermore, addressing regulatory challenges will enable the clinical application of sustainable, patient-focused treatments for MS. By filling current gaps, future studies could fully exploit their potential in treating MS and other demyelinating conditions.