Ocular pharmacokinetics of econazole solid lipid nanoparticle eye drops after single dose topical administration in rabbits

Authors: Liang Zhen,  Zhang Zhen,  Li Jingguo,  Yang Jingjing,  Lu Ping,  Zhou Tianyang,  Zhang Junjie

DOI: 10.3760/cma.j.cn115989-20191008-00429
Published 2020-12-10
Cite as Chin J Exp Ophthalmol, 2020,38(12): 1032-1037.

Abstract

Objective

To investigate the pharmacokinetics of econazole solid lipid nanoparticles (E-SLNs) after administration of one single dose in rabbit eyes.

Methods

E-SLNs with 0.2% econazole was prepared by microemulsion method.Its antifungal activity against Fusarium isolated from the eyes of patients with fungal keratitis was evaluated in vitro and was compared with natamycin eye drops.Four healthy New Zealand white rabbits were assigned to the blank control group without any drug interference during the experimental period, and other matched 21 rabbits were randomized into 7 groups according to the specimen-collected time, with 3 rabbits in each group.E-SLNs of 50 μl was singly applied to conjunctival sac in both eyes in the 21 rabbits, and tear was collected using a filter paper at 5, 15, 30, 60, 90, 120 and 180 minutes following administration of the drug.The cornea specimen was collected at above-mentioned time points respectively.The drug levels in each sample were assayed by high performance liquid chromatography.The accuracy, recovery rate, stability and antifungal activity of the drugs in tear fluid and cornea were detected.This study protocol was approved by the Life Science Ethics Review Committee of Henan Eye Hospital (No.HENNCA-2017-22).

Results

For the tear samples and corneal tissue samples, the relative standard deviation (RSD) of the accuracy of the drug was 2.34%-4.04%; the stability analysis result showed that the RSD of the drugs was less than 10%.The 50% minimum inhibitory concentration (MIC50) and 90% minimum inhibit concentration (MIC90) of E-SLNs were 0.37 μg/ml and 0.89 μg/ml, respectively.The MIC50 and MIC90 of natamycin were 1.15 μg/ml and 1.70 μg/ml, respectively.After one single dose application of E-SLNs eye drops, the peak time of the drug in tears fluids and cornea of rabbits were 5 minutes and maximum concentrations in tears and cornea were 597.64 μg/g and 33.15 μg/g, respectively.

Conclusions

The drug levels in tears and cornea achieved are higher than MIC against Fusarium.

Key words:

Solid lipid nanoparticles; Econazole; Ocular pharmacokinetics

Contributor Information

Liang Zhen
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhenzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
Zhang Zhen
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhenzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
Li Jingguo
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhenzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
Yang Jingjing
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhenzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
Lu Ping
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhenzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
Zhou Tianyang
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhenzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
Zhang Junjie
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhenzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
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Updated: December 18, 2020 — 8:10 am