RT Journal Article
T1 Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil.
A1 Espinoza, Lupe Carolina
A1 Silva-Abreu, Marcelle
A1 Clares, Beatriz
A1 Rodríguez-Lagunas, María José
A1 Halbaut, Lyda
A1 Cañas, María-Alexandra
A1 Calpena, Ana Cristina
K1 Alzheimer’s disease
K1 Donepezil
K1 Pluronic F-127
K1 mucoadhesion
K1 nanoemulsion
K1 nose-to-brain
AB 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.
SN 1999-4923
YR 2019
FD 2019-02-01
LK https://hdl.handle.net/10668/28137
UL https://hdl.handle.net/10668/28137
LA en
DS RISalud
RD Apr 8, 2025