CHITOSAN-COATED POLYMERIC NANOPARTICLES FOR ALZHEIMER'S DISEASE
Abstract
Alzheimer's disease remains a formidable therapeutic challenge, largely due to the blood brain barrier restricting drug access to the central nervous system. We systematically synthesize preclinical evidence on chitosan-coated polymeric nanoparticles as a non invasive intranasal delivery platform for targeted Alzheimer's therapy. Our central hypothesis is that the mucoadhesive and permeation-enhancing properties of chitosan coatings can significantly improve brain bioavailability and neurotherapeutic efficacy of both synthetic drugs and natural compounds. We conducted a systematic literature search in PubMed, Scopus, and Web of Science for studies published from 2010 onward, extracting data on nanoparticle physicochemical properties, cellular uptake, neuroimmune modulation, and pharmacokinetics. The retrieved studies exhibited substantial heterogeneity in core materials but consistently demonstrated that chitosan-coated systems enhanced brain targeted delivery. For instance, a mannose-functionalized chitosan-coated PLGA system co-delivering cannabidiol and BDNF plasmid achieved a zeta potential of +31.7 mV and particle size of 306 nm, while a chitosan-coated liposomal donepezil system showed the highest cellular uptake efficiency of 66.8%. Neuroimmune modulation was evidenced by curcumin-encapsulated chitosan-coated PLGA nanoparticles reducing tumor necrosis factor-alpha levels to 70% of the positive control in BV-2 microglial cells. Furthermore, in vivo studies with synaptic acid-loaded chitosan-solid lipid nanoparticles in amyloid-betainduced mice reported a 1.7-fold increase in drug half-life and improved cognition. However, critical translational gaps emerged: standardized muco adhesion metrics in primary human nasal epithelial cells under flow conditions were absent, comprehensive profiling of microglial and astrocytic polarization shifts in aged models was not performed, and no direct proteomic comparison of cerebrospinal fluid-derived versus plasma-derived protein corona was retrieved. Moreover, ex vivo hippocampal slice studies linking synaptic plasticity to nanoparticle exposure were lacking, and circadian glymphatic clearance mapping in freely moving animals remained unreported.
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