Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil Espinoza, Lupe Carolina Clares Naveros, Beatriz Donepezil Nanoemulsion Mucoadhesion Nose-to-brain Pluronic F-127 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. 2020-01-23T09:17:28Z 2020-01-23T09:17:28Z 2019-02-01 info:eu-repo/semantics/article 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. http://hdl.handle.net/10481/59054 10.3390/pharmaceutics11020064 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI