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Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil
Donepezil (DPZ) is widely used in the treatment of Alzheimer’s disease in tablet form for oral administration. The pharmacological efficacy of this drug can be enhanced by the use of intranasal administration because this route makes bypassing the blood–brain barrier (BBB) possible. The aim of this...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410084/ https://www.ncbi.nlm.nih.gov/pubmed/30717264 http://dx.doi.org/10.3390/pharmaceutics11020064 |
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author | Espinoza, Lupe Carolina Silva-Abreu, Marcelle Clares, Beatriz Rodríguez-Lagunas, María José Halbaut, Lyda Cañas, María-Alexandra Calpena, Ana Cristina |
author_facet | Espinoza, Lupe Carolina Silva-Abreu, Marcelle Clares, Beatriz Rodríguez-Lagunas, María José Halbaut, Lyda Cañas, María-Alexandra Calpena, Ana Cristina |
author_sort | Espinoza, Lupe Carolina |
collection | PubMed |
description | Donepezil (DPZ) is widely used in the treatment of Alzheimer’s disease in tablet form for oral administration. The pharmacological efficacy of this drug can be enhanced by the use of intranasal administration because this route makes bypassing the blood–brain barrier (BBB) possible. The aim of this study was to develop a nanoemulsion (NE) as well as a nanoemulsion with a combination of bioadhesion and penetration enhancing properties (PNE) in order to facilitate the transport of DPZ from nose-to-brain. Composition of NE was established using three pseudo-ternary diagrams and PNE was developed by incorporating Pluronic F-127 to the aqueous phase. Parameters such as physical properties, stability, in vitro release profile, and ex vivo permeation were determined for both formulations. The tolerability was evaluated by in vitro and in vivo models. DPZ-NE and DPZ-PNE were transparent, monophasic, homogeneous, and physically stable with droplets of nanometric size and spherical shape. DPZ-NE showed Newtonian behavior whereas a shear thinning (pseudoplastic) behavior was observed for DPZ-PNE. The release profile of both formulations followed a hyperbolic kinetic. The permeation and prediction parameters were significantly higher for DPZ-PNE, suggesting the use of polymers to be an effective strategy to improve the bioadhesion and penetration of the drug through nasal mucosa, which consequently increase its bioavailability. |
format | Online Article Text |
id | pubmed-6410084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64100842019-03-29 Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil Espinoza, Lupe Carolina Silva-Abreu, Marcelle Clares, Beatriz Rodríguez-Lagunas, María José Halbaut, Lyda Cañas, María-Alexandra Calpena, Ana Cristina Pharmaceutics Article Donepezil (DPZ) is widely used in the treatment of Alzheimer’s disease in tablet form for oral administration. The pharmacological efficacy of this drug can be enhanced by the use of intranasal administration because this route makes bypassing the blood–brain barrier (BBB) possible. The aim of this study was to develop a nanoemulsion (NE) as well as a nanoemulsion with a combination of bioadhesion and penetration enhancing properties (PNE) in order to facilitate the transport of DPZ from nose-to-brain. Composition of NE was established using three pseudo-ternary diagrams and PNE was developed by incorporating Pluronic F-127 to the aqueous phase. Parameters such as physical properties, stability, in vitro release profile, and ex vivo permeation were determined for both formulations. The tolerability was evaluated by in vitro and in vivo models. DPZ-NE and DPZ-PNE were transparent, monophasic, homogeneous, and physically stable with droplets of nanometric size and spherical shape. DPZ-NE showed Newtonian behavior whereas a shear thinning (pseudoplastic) behavior was observed for DPZ-PNE. The release profile of both formulations followed a hyperbolic kinetic. The permeation and prediction parameters were significantly higher for DPZ-PNE, suggesting the use of polymers to be an effective strategy to improve the bioadhesion and penetration of the drug through nasal mucosa, which consequently increase its bioavailability. MDPI 2019-02-01 /pmc/articles/PMC6410084/ /pubmed/30717264 http://dx.doi.org/10.3390/pharmaceutics11020064 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Espinoza, Lupe Carolina Silva-Abreu, Marcelle Clares, Beatriz Rodríguez-Lagunas, María José Halbaut, Lyda Cañas, María-Alexandra Calpena, Ana Cristina Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil |
title | Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil |
title_full | Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil |
title_fullStr | Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil |
title_full_unstemmed | Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil |
title_short | Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil |
title_sort | formulation strategies to improve nose-to-brain delivery of donepezil |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410084/ https://www.ncbi.nlm.nih.gov/pubmed/30717264 http://dx.doi.org/10.3390/pharmaceutics11020064 |
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