Title:Intranasal Lipid Particulate Drug Delivery Systems: An Update on Clinical Challenges and Biodistribution Studies of Cerebroactive Drugs in Alzheimer’s disease
Volume: 26
Issue: 27
Author(s): Deepshi Arora, Shailendra Bhatt , Manish Kumar, Hari D.C. Vattikonda, Yugam Taneja, Vishal Jain, Veenu Joshi and Chaitanya C. Gali*
Affiliation:
- Institute of Immunology and Pathophysiology, Otto Loewi Research Center, Medical University of Graz,Austria
Keywords:
Intranasal, clinical, Alzheimer, bio-distribution, histopathology, lipid carriers.
Abstract: Background: Alzheimer's is the primary cause of death in the various countries that affect wide strata
of the population. The treatment of it is restricted to a few conventional oral medications that act only superficially.
It is evident that the delivery of a drug to the brain across the blood-brain barrier is challenging as the BBB
is armed with several efflux transporters like the P-glycoprotein as well as nasal mucociliary clearance adds up
leading to decreased concentration and reduced therapeutic efficacy. Considering these, the intranasal IN route of
drug administration is emerging as an alternative route for the systemic delivery of a drug to the brain. The intranasal
(IN) administration of lipid nanoparticles loaded with cerebroactive drugs showed promise in treating various
neurodegenerative diseases, since the nasal route allows the direct nose to brain delivery by means of solid
lipid nanoparticles (SLN’s). The tailoring of intranasal lipid particulate drug delivery systems is a pleasing approach
to facilitate uptake of therapeutic agents at the desired site of action, particularly when a free drug has
poor pharmacokinetics/ biodistribution (PK/BD) or significant off-site toxicities.
Objectives: 1) In this review, key challenges and physiological mechanisms regulating intranasal brain delivery in
Alzheimer’s disease, ex vivo studies, pharmacokinetics parameters including brain uptake and histopathological
studies are thoroughly discussed.
2) A thorough understanding of the in vivo behaviour of the intranasal drug carriers will be the elusive goal.
3) The article emphasizes to drag the attention of the research community working in the intranasal field towards
the challenges and hurdles of the practical applicability of intranasal delivery of cerebroactive drugs.
Method: Various electronic databases, journals like nanotechnology and nanoscience, dove press are reviewed for
the collection and compilation of data.
Results: From in vivo biodistribution studies, pharmacokinetics parameters, and gamma scintigraphy images of
various drugs, it is speculated that intranasal lipid particulates drug delivery system shows better brain targeting
efficiency for various CNS disorders in comparison to other routes.
Conclusion: Various routes are explored for the delivery of drugs to increase bioavailability in the brain for CNS
disorders but the intranasal route shows better results that pave the way for success in the future if properly explored.