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Author: Admin | 2025-04-28
Chitosan powder, and chitosan microspheres [13,19,41,[51][52][53][54]. ...... The absence of chitosan toxicity in nasal epithelia has been confirmed in several animal studies (up to 28 days) as well as clinical trials (7 days), with no interference on nasal cilia beat frequency and bio-membranes [41,52,56,60]. As such, chitosan has been adopted as a carrier matrix to prepare different nasal formulations, including hydrogels, thermosensitive in-situ gel, interpenetrating gel of glutaraldehyde-crosslinked chitosan, chitosan aqueous solution, chitosan powder, and chitosan microspheres [13,19,41,[51][52][53][54]. The discrepancy in the effectiveness of a copolymer in tight junction opening and bioavailability can be explained by the different polymer concentrations, molecular weight, chemical conjugation, degree of deacetylation, and the ratio of drug and polymer [32,51,61]. ...This comprehensive review delves into the potential of intranasal insulin delivery for managing Alzheimer's Disease (AD) while exploring the connection between AD and diabetes mellitus (DM). Both conditions share features of insulin signalling dysregulation and oxidative stress that accelerate inflammatory response. Given the physiological barriers to brain drug delivery, including the blood-brain barrier, intranasal administration emerges as a non-invasive alternative. Notably, intranasal insulin has shown neuroprotective effects, impacting Aβ clearance, tau phosphorylation, and synaptic plasticity. In preclinical studies and clinical trials, intranasally administered insulin achieved rapid and extensive distribution throughout the brain, with optimal formulations exhibiting minimal systemic circulation. The detailed mechanism of insulin transport through the nose-to-brain pathway is elucidated in the review, emphasizing the role of olfactory and trigeminal nerves. Despite promising prospects, challenges in delivering protein drugs from the nasal cavity to the brain remain, including enzymes, tight junctions, mucociliary clearance, and precise drug deposition, which hinder its translation to clinical settings. The review encompasses a discussion of the strategies to enhance the intranasal delivery of therapeutic proteins, such as tight junction modulators, cell-penetrating peptides, and nano-drug carrier systems. Moreover, successful translation of nose-to-brain drug delivery necessitates a holistic understanding of drug transport mechanisms, brain anatomy, and nasal formulation optimization. To date, no intranasal insulin formulation has received regulatory approval for AD treatment. Future research should address challenges related to drug absorption, nasal deposition, and the long-term effects of intranasal insulin. In
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