Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion.
Regul Toxicol Pharmacol
; 82: 20-31, 2016 Dec.
Article
en En
| MEDLINE
| ID: mdl-27815174
ABSTRACT
Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 µg/mL, 0.333 ± 0.071 µg/mL and 0.217 ± 0.062 µg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Aceites
/
Portadores de Fármacos
/
Agua
/
Bloqueadores del Receptor Tipo 1 de Angiotensina II
/
Nanopartículas
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Olmesartán Medoxomilo
/
Antihipertensivos
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Regul Toxicol Pharmacol
Año:
2016
Tipo del documento:
Article