The liquid crystalline phase behaviour of a nasal formulation modifies the brain disposition of donepezil in rats in the treatment of Alzheimer's disease.

Autor: de Souza IFF; Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas, MG, Brazil. Electronic address: isabelly.souza@sou.unifal-mg.edu.br., Dos Santos TQ; Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas, MG, Brazil. Electronic address: tahqueirozs@gmail.com., Placido RV; Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas, MG, Brazil. Electronic address: rodrigo.placido@sou.unifal-mg.edu.br., Mangerona BA; Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas, MG, Brazil. Electronic address: bi.mangerona@gmail.com., Carvalho FC; Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas, MG, Brazil. Electronic address: flavia.chiva@unifal-mg.edu.br., Boralli VB; Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas, MG, Brazil. Electronic address: vanessa.marques@unifal-mg.edu.br., Ruela ALM; Pharmacy School, Federal University of Ouro Preto, Ouro Preto, MG, Brazil. Electronic address: andre.ruela@ufop.edu.br., Pereira GR; Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas, MG, Brazil. Electronic address: gislaine.pereira@unifal-mg.edu.br.
Jazyk: angličtina
Zdroj: Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2021 Jul; Vol. 203, pp. 111721. Date of Electronic Publication: 2021 Mar 24.
DOI: 10.1016/j.colsurfb.2021.111721
Abstrakt: Although nanoparticles, polymeric micelles, liposomes, nanoemulsions, and microemulsions were extensively evaluated as formulations for nasal administration of drugs, lyotropic liquid crystal (LLC) mesophases have been few studied. The phase transition from a low-viscosity microemulsion to a more viscous LLC may improve the mucoadhesion of the formulation. Donepezil is a drug administered orally in the treatment of Alzheimer's disease, and with gastrointestinal side effects that are typical of acetylcholinesterase inhibitors. Based on this, donepezil administration by nasal pathway using a mucoadhesive LLC may be a feasible alternative. A colloidal formulation was selected from a ternary diagram, combining CETETH-10, oleic acid, and water (40:45:15, w/w). Donepezil was incorporated into the formulation, and the characterisation included in vitro studies, such as mucoadhesion and drug release. Pharmacokinetics in Wistar rats included evaluations by the nasal pathway with donepezil incorporated into microemulsion. A phase transition from an isotropic to an anisotropic system was observed after the swelling of the microemulsion with artificial nasal fluid (12-20 %). The release of donepezil in vitro occurred in a sustained manner. Significant levels of donepezil were achieved in the brain after nasal administration of the microemulsion, as a promising strategy for the treatment of Alzheimer's disease.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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