Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion

Autor: Bapi Gorain, Saumen Karan, Tapan Kumar Pal, Rakesh K. Tekade, Parasuraman Jaisankar, Hira Choudhury
Rok vydání: 2016
Předmět:
Male
Angiotensin receptor
Biodistribution
Drug Compounding
Drinking
Administration
Oral
02 engineering and technology
Pharmacology
Toxicology
Risk Assessment
030226 pharmacology & pharmacy
Permeability
Eating
03 medical and health sciences
0302 clinical medicine
Tandem Mass Spectrometry
Oral administration
medicine
Animals
Tissue Distribution
Rats
Wistar
Adverse effect
Antihypertensive Agents
Drug Carriers
Olmesartan Medoxomil
business.industry
Body Weight
Toxicity Tests
Subchronic
Brain
Reproducibility of Results
Water
Organ Size
General Medicine
021001 nanoscience & nanotechnology
Bioavailability
Nanomedicine
Pharmacodynamics
Toxicity
Nanoparticles
Emulsions
0210 nano-technology
Olmesartan
business
Angiotensin II Type 1 Receptor Blockers
Oils
Biomarkers
Chromatography
Liquid
medicine.drug
Zdroj: Regulatory Toxicology and Pharmacology. 82:20-31
ISSN: 0273-2300
DOI: 10.1016/j.yrtph.2016.10.020
Popis: 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.
Databáze: OpenAIRE
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