Bifunctional Chitosan-Based Nanocarriers As Promising Therapeutic Approach for Brain Disease Therapy: A Critical Review Focusing on Multiple Sclerosis Over Emerging Strategies, Technologies and Applications Publisher Pubmed



Naghib SM ; Khorasani MA ; Sharifianjazi F ; Tavamaishvili K
Source: International Journal of Biological Macromolecules Published:2025

Abstract

Chitosan (CS) has appeared as a promising candidate in brain disease (BD) (such as Alzheimer's, Parkinson's, and Multiple sclerosis (MS)) therapy due to its anti-inflammatory, antioxidative, and neuroprotective properties. CS's capacity to interact with the blood-brain barrier (BBB) enhances the central nervous system (CNS) drug permeability, offering new avenues for effective treatment strategies aimed at overcoming the limitations of conventional therapies. Furthermore, CS's role in regenerative medicine extends beyond drug delivery, as it fosters neural repair by providing a supportive microenvironment for oligodendrocyte proliferation and neuronal regeneration. Studies have shown that CS-based scaffolds, when combined with neurotrophic factors and stem cells, can enhance remyelination and neuroprotection in BD models. The immunomodulatory effects of CS further contribute to reducing neuroinflammation by shifting immune responses toward an anti-inflammatory phenotype, thereby mitigating the progression of BD-associated damage. This review provides a comprehensive analysis of the latest advancements in CS-based BD therapies, exploring its multifunctional applications in drug delivery, immune modulation, and tissue engineering. The discussion also addresses the current challenges in clinical translation, including variability in CS formulations, regulatory considerations, and potential safety concerns. Future research directions should focus on optimizing CS derivatives, improving its bioavailability, and integrating it with emerging therapeutic approaches such as gene therapy and biomimetic nanocarriers. © 2025 Elsevier B.V., All rights reserved.