Coated Lipidic Nanoparticles as a New Strategy for Enhancing Nose-to-Brain Delivery of a Hydrophilic Drug Molecule
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Date
4/19/2020
Authors
Salem, L.H
El-Feky, G.S
Fahmy, R.H
El Gazayerly, O.N
Abdelbary, A
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Elsevier B.V.
Series Info
Journal of Pharmaceutical Sciences;
Scientific Journal Rankings
Abstract
Oral Almotriptan maleate (ALM) is used in the treatment of migraine; however, due to its extreme aqueous solubility, shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. Being flexible and lipophilic in nature, nanostructured lipid carriers (NLCs) represent a promising tool in delivering therapeutic substances to the brain. This investigation is meant to explore the capability of mucoadhesive chitosan-coated NLCs to efficiently deliver ALM to the brain through the nasal route as a non-invasive alternative route for targeting the central nervous system (CNS). D-optimal design was adopted and thirteen different formulae were prepared using hot homogenization and ultrasonication technique; where an accurate amount of the almotriptan was added to the molten lipid mixture followed by the addition of the heated aqueous phase under stirring, then the mixture was subjected to homogenization and ultrasonication. The prepared systems were then assessed for their particle size, PDI (polydispersity index), zeta potential (ZP), and entrapment efficiency (EE). The optimized selected formula; F1; composed of 50/50 Compritol/Labrafil and a co-mixture of 2:1 tween 80: Lauroglycol all coated in chitosan, showed a PS of 255 nm, PDI 0.27, ZP 34.1 mV, and 80% EE. A bi-phasic in-vitro drug release pattern was obtained, enhanced mucoadhesive property and ex-vivo permeability through sheep nasal mucosa were attained. The In-vivo studies performed on albino rabbits showed significantly higher Cmax results in plasma of the optimized ALM-NLC (1.54 μg/mL) compared to those of IN ALM solution (0.25 μg/mL) and ALM oral tablet market product (0.58 μg/mL). Brain Cmax were found to be 3.64 μg/mL, 0.5 μg/mL and 0.48 μg/mL for IN ALM-NLC, oral ALM market product and, IN ALM solution, respectively. Histopathological examination marked the formula as safe
Description
Scopus
Keywords
Almotriptan, Biodistribution, Nanostructured lipid carriers, Intranasal, Mucoadhesion, Nasal histopathology
Citation
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