Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil
Metadatos
Afficher la notice complèteEditorial
MDPI
Materia
Donepezil Nanoemulsion Mucoadhesion Nose-to-brain Pluronic F-127
Date
2019-02-01Referencia bibliográfica
Espinoza, L. C., Silva-Abreu, M., Clares, B., Rodríguez-Lagunas, M. J., Halbaut, L., Cañas, M. A., & Calpena, A. C. (2019). Formulation strategies to improve nose-to-brain delivery of donepezil. Pharmaceutics, 11(2), 64.
Patrocinador
This research was funded by the Secretaría de Educación Superior, Ciencia, Tecnología e Innovación (SENESCYT—Ecuador).Résumé
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.