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

Abstract

Background 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. Methods 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 ( R 2 >0.999). Results 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. Conclusion 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.

Development of a Novel Nano­emulsion Formulation to Improve Intestinal Absorption of Cannabidiol

“…Self-micro- or self-nano-emulsifying drug delivery systems can produce nanoemulsion (NE) and improve the oral bioavailability of highly lipophilic compounds [18-20]. NE formulations comprise ternary phases: oil, water, and surfactant.…”

The efficacy of microemulsion-based delivery to improve vitamin E properties: evaluation of the antinociceptive, antioxidant, antidepressant- and anxiolytic-like activities in mice

“…Indeed, ME have been shown to increase the bioavailability and efficacy of a variety of natural compounds, such as camptocethin analogues, taxanes, vinca alkaloid and flavonoids. [52][53][54] Moreover, the attractive effects of VE-ME in subchronic treatment were more pronounced than that observed in acute treatment. This result could be explained due to the controlled release of VE from the ME system.…”

“…In fact, the distribution of a substance in the body is essentially determined by its physicochemical properties and is correlated with its pharmacological effects. ME may promote modified drug release, increasing gastrointestinal distribution and protecting against chemical and enzymatic degradation . In addition, ME is expected to afford an efficient delivery of therapeutic agents to target sites in the body due to the small droplets size.…”

“…In addition, ME is expected to afford an efficient delivery of therapeutic agents to target sites in the body due to the small droplets size. Indeed, ME have been shown to increase the bioavailability and efficacy of a variety of natural compounds, such as camptocethin analogues, taxanes, vinca alkaloid and flavonoids . Moreover, the attractive effects of VE‐ME in subchronic treatment were more pronounced than that observed in acute treatment.…”

“…ME may promote modified drug release, increasing gastrointestinal distribution and protecting against chemical and enzymatic degradation. [52] In addition, ME is expected to afford an efficient delivery of therapeutic agents to target sites in the body due to the small droplets size. Indeed, ME have been shown to increase the bioavailability and efficacy of a variety of natural compounds, such as camptocethin analogues, taxanes, vinca alkaloid and flavonoids.…”