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Int J Nanomedicine. 2018 Jan 31;13:669-680. doi: 10.2147/IJN.S154824. eCollection 2018.

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

Author information

1
School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
2
Chinese Medicine Department, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi City, Taiwan.
3
PhD Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
4
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

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 (R2>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.

KEYWORDS:

andrographolide; intestinal permeability; nanoemulsion; oral bioavailability

PMID:
29440893
PMCID:
PMC5798547
DOI:
10.2147/IJN.S154824
[Indexed for MEDLINE]
Free PMC Article

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