Application of chitosan-based nano-drugs in the treatment of brain diseases

<sec><p indent="0mm">The blood-brain barrier (BBB), an exquisitely selective semipermeable interface, operates as a potent safeguard, vigilantly shielding the central nervous system (CNS) from deleterious substances within the bloodstream. This intricate physiological bulwark, constituted by brain capillary endothelial cells, astrocytes, pericytes, and a basal lamina, stringently governs the molecular flux, thereby preserving the homeostasis of the CNS. However, paradoxically, this protective role of the BBB has inadvertently metamorphosed into a substantial encumbrance within the purview of brain disease therapeutics. The BBB curtails the ingress of numerous therapeutic agents, spanning from small molecule pharmaceuticals to large biomolecular entities, into the brain, thereby gravely impeding the efficacy of treatment regimens for a broad spectrum of neurological maladies, including gliomas, neurodegenerative afflictions (Alzheimer’s and Parkinson’s diseases), ischemic stroke, and traumatic brain injury. </sec><sec> In recent epochs, nanotechnology has surfaced as a formidable arsenal in the quest to surmount the BBB conundrum. Chitosan, a naturally sourced polysaccharide derived from chitin, has amassed considerable intrigue within the domain of drug delivery, attributable to its exceptional biodegradability, biocompatibility, low immunogenicity, and mucoadhesive attributes. This review undertakes an exhaustive exploration of the application of chitosan-based nanomedicines in the amelioration of diverse brain disorders. </sec><sec> Chitosan-based nanocarriers proffer several distinctive merits in the realm of drug conveyance. Their diminutive size and augmented surface area-to-volume ratio capacitate them to engage with the BBB in a more efficacious manner. Chemical modifications of chitosan, such as phosphorylation, carboxymethylation, and quaternization, not only augment its solubility but also endow it with supplementary advantageous characteristics, encompassing enhanced drug loading capacity and regulated release kinetics. These nanocarriers can be further embellished with an array of ligands, including peptides and antibodies, to actualize active targeting to specific brain regions or cellular entities. </sec><sec> In the context of glioma treatment, chitosan nanoparticles have been adroitly exploited to encapsulate and ferry chemotherapeutic agents, augmenting their cytotoxic potency against cancer cells while concomitantly attenuating systemic side effects. In the arena of neurodegenerative diseases, chitosan-based nanomedicines have evinced promise in transporting drugs and genetic materials to modulate the pathophysiological processes associated with Alzheimer’s and Parkinson’s diseases, such as amyloid-beta deposition and alpha-synuclein aggregation. For ischemic stroke and traumatic brain injury, chitosan carriers have been enlisted to deliver neurotrophic factors and stem cells, thereby fostering tissue repair, angiogenesis, and functional restitution. </sec><sec> Notwithstanding the remarkable strides accomplished hitherto, several hurdles still await resolution. The stability of chitosan-based nanocarriers within the complex physiological milieu of the bloodstream mandates further refinement to guarantee efficient drug delivery. The precise mechanistic underpinnings governing the translocation of chitosan nanoparticles across the BBB and their interactions with brain cells remain only partially elucidated and necessitate in-depth scrutiny. Additionally, the evolution of more refined and stimuli-responsive nanocarriers for controlled drug release at the target locus represents an active area of research inquiry. </sec>