Journal Article

Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide

Chen, Yi-Chen, Wang, Chia-Chi, Yen, Ching-Chi, Wu, Yu-Tse, Wu, Ming-Tsang

2018

Overview

Andrographolide (AG), a compound with low water solubility, possesses various pharmacological activities, particularly anti-inflammatory activity. However, its low oral bioavailability is a major obstacle to its potential use. This study developed and optimized an AG-loaded nanoemulsion (AG-NE) formulation to improve AG oral bioavailability and its protective effects against inflammatory bowel disease. A high-pressure homogenization technique was used to prepare the AG-NE and solubility, viscosity, and droplet size tests were conducted to develop the optimized AG-NE composed of α-tocopherol, ethanol, Cremophor EL, and water. The permeability was assessed using everted rat gut sac method and in vivo absorption and anti-inflammatory effect in rats was also evaluated. The plasma concentration of AG was determined using our validated high performance liquid chromatography method, which was used to generate a linear calibration curve over the concentration range of 0.1-25 μg/mL in rat plasma ( >0.999). The optimized AG-NE had a droplet size of 122±11 nm confirmed using transmission electron microscopy and a viscosity of 28 centipoise (cps). It was stable at 4 and 25°C for 90 days. An ex vitro intestinal permeability study indicated that the jejunum was the optimal site for AG absorption from the optimized AG-NE, which was 8.21 and 1.40 times higher than that from an AG suspension and AG ethanol solution, respectively. The pharmacokinetic results indicate that the absorption of AG from AG-NE was significantly enhanced in comparison with that from the AG suspension, with a relative bioavailability of 594.3%. Moreover, the ulcer index and histological damage score of mice with indomethacin-induced intestinal lesions were significantly reduced by AG-NE pretreatment. We conclude that the developed AG-NE not only enhanced the oral bioavailability of AG in this study but may also prove to be an effective formulation of AG for preventing gastrointestinal inflammatory disorders.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Medical Press
• Subject: Administration, Oral / alpha-Tocopherol - chemistry / andrographolide / Animals / Anti-inflammatory agents / Anti-Inflammatory Agents, Non-Steroidal - administration & dosage / Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics / Bioavailability / Biological Availability / Chromatography / Diterpenes - administration & dosage / Diterpenes - pharmacokinetics / Drug delivery systems / Electron microscopy / Emulsions - administration & dosage / Emulsions - chemistry / Enteritis - chemically induced / Enteritis - drug therapy / Ethanol / Food / Gastrointestinal diseases / Glycoproteins / High performance liquid chromatography / Homogenization / Indomethacin / Indomethacin - adverse effects / Inflammation / Inflammatory bowel disease / intestinal permeability / Liquid chromatography / Male / Methods / Mice, Inbred C57BL / Microscopy / nanoemulsion / Nanoemulsions / Nanoparticles / Nanoparticles - chemistry / Nanostructures - administration & dosage / Nanostructures - chemistry / oral bioavailability / Original Research / Permeability / Pharmacy / Rats, Sprague-Dawley / Solubility / Surfactants / Tocopherols / Tumor necrosis factor-TNF / Viscosity / Vitamin E / Water / Water - chemistry