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Review
. 2022 Sep 13:13:979682.
doi: 10.3389/fphar.2022.979682. eCollection 2022.

Nasal delivery of neurotherapeutics via nanocarriers: Facets, aspects, and prospects

Amarjitsing Rajput  1 , Prashant Pingale  2 , Vividha Dhapte-Pawar  1
Affiliations
Review

Nasal delivery of neurotherapeutics via nanocarriers: Facets, aspects, and prospects

Amarjitsing Rajput et al. Front Pharmacol. .

Abstract

Alzheimer's disease (AD) is one of the neurological ailments which continue to represent a major public health challenge, owing to increased life expectancy and aging population. Progressive memory loss and decrease in cognitive behavior, owing to irreversible destruction of neurons along with expensive therapeutic interventions, call for an effective, alternate, yet affordable treatment for Alzheimer's disease. Safe and effective delivery of neurotherapeutics in Alzheimer's like central nervous system (CNS) disorders still remains elusive despite the major advances in both neuroscience and drug delivery research. The blood-brain barrier (BBB) with its tight endothelial cell layer surrounded by astrocyte foot processes poses as a major barrier for the entry of drugs into the brain. Nasal drug delivery has emerged as a reliable method to bypass this blood-brain barrier and deliver a wide range of neurotherapeutic agents to the brain effectively. This nasal route comprises the olfactory or trigeminal nerves originating from the brain and terminating into the nasal cavity at the respiratory epithelium or olfactory neuroepithelium. They represent the most direct method of noninvasive entry into the brain, opening the most suitable therapeutic avenue for treatment of neurological diseases. Also, drugs loaded into nanocarriers can have better interaction with the mucosa that assists in the direct brain delivery of active molecules bypassing the BBB and achieving rapid cerebrospinal fluid levels. Lipid particulate systems, emulsion-based systems, vesicular drug delivery systems, and other nanocarriers have evolved as promising drug delivery approaches for the effective brain delivery of anti-Alzheimer's drugs with improved permeability and bioavailability via the nasal route. Charge, size, nature of neurotherapeutics, and formulation excipients influence the effective and targeted drug delivery using nanocarriers via the nasal route. This article elaborates on the recent advances in nanocarrier-based nasal drug delivery systems for the direct and effective brain delivery of the neurotherapeutic molecules. Additionally, we have attempted to highlight various experimental strategies, underlying mechanisms in the pathogenesis and therapy of central nervous system diseases, computational approaches, and clinical investigations pursued so far to attain and enhance the direct delivery of therapeutic agents to the brain via the nose-to-brain route, using nanocarriers.

Keywords: Alzheimer’s disease; brain-targeted drug delivery; intranasal formulations; nanocarrier; neurotherapeutics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Intranasal drug delivery mechanisms for brain targeting.
FIGURE 2
FIGURE 2
Diverse nanocarriers for the effective nose-to-brain delivery in Alzheimer’s treatment.
See this image and copyright information in PMC

References

    1. Abbott N. J., Rönnbäck L., Hansson E. (2006). Astrocyte–endothelial interactions at the blood–brain barrier. Nat. Rev. Neurosci. 7 (1), 41–53. 10.1038/nrn1824 - DOI - PubMed
    1. Ageing W. P. (2021). “United nations department of economic and social affairs, population division,” in World population ageing 2020 highlights: Living arrangements of older persons (New York: UN, 2021; ). Available at: https://www.un.org/development/desa/pd/sites/www.un.org.development.desa... Accessed on April 4, 2021).
    1. Agrawal M., Saraf S., Saraf S., Antimisiaris S. G., Chougule M. B., Shoyele S. A., et al. (2018). Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs. J. Control. Release 281, 139–177. 10.1016/j.jconrel.2018.05.011 - DOI - PubMed
    1. Al Harthi S., Alavi S., Radwan M. A., El Khatib M. M., Al Sarra I. A. (2019). Nasal delivery of donepezil HCl-loaded hydrogels for the treatment of Alzheimer’s disease. Sci. Rep. 9 (1), 9563–9620. 10.1038/s41598-019-46032-y - DOI - PMC - PubMed
    1. Aliev G., Ashraf G., Tarasov V. N., Chubarev V. N., Leszek J., Gasiorowski K., et al. (2019). Alzheimer's disease - future therapy based on dendrimers. Curr. Neuropharmacol. 17 (3), 288–294. 10.2174/1570159X16666180918164623 - DOI - PMC - PubMed