Ocular pharmacokinetics of topical administration of butenafine nanomicelles in rabbit eyes

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

DOI: 10.3760/cma.j.cn115989-20200526-00374
Published 2020-12-10
Cite as Chin J Exp Ophthalmol, 2020,38(12): 1038-1044.

Abstract

Objective

To study the pharmacokinetics of the broad-spectrum antifungal drug butenafine nanomicelles (BTF-NM) after topical instillation.

Methods

The self-assembly method was used to prepare BTF-NM.The particle size, Zeta potential, and polydispersity index (PDI) of BTF-NM were measured by a nano-particle size-Zeta potential analyzer, and the encapsulation efficiency was determined by high-performance liquid chromatography (HPLC). Forty-two healthy New Zealand white rabbits without eye disease were randomly divided into the BTF-NM group and the BTF suspension (BTF-S) group.The corresponding drugs were instilled in the conjunctival sac with a single instillation of 50 μl.The 7.5 mm filter paper was placed in the conjunctival sac of rabbit eye for 1 minute at 5, 15, 30, 60, 120, 180, 240 minutes after the administration.Then the rabbits were sacrificed by intravenous injection of 4% sodium pentobarbital solution through the ears of the rabbits.The aqueous humor was extracted and the corneal tissue was dissected.The drug concentration of BTF in different tissues was measured by HPLC.The study was approved by the Life Science Ethics Review Committee of Henan Eye Hospital (No.HNEECA-2019-01).

Results

The particle size and PDI of BTF-NM were (15.65±0.04)nm and 0.11±0.01, respectively, the Zeta potential was (-0.29±0.36)mV, the encapsulation rate was (98.38±0.29)%.The peak time of the drug both in tears and corneal tissues after BTF-NM application was 5 minutes.The peak concentrations of the drug in tears and corneas of the BTF-NM group were (485.21±66.29) μg/g and (12.53±2.32) μg/g, which were 5.6 and 78 times than that of the BTF-S group, respectively.Within the observation time, the mass fractions of the drug in tears and corneas of the BTF-NM group at each time point were significantly higher than those of BTF-S group at corresponding time points (all at P<0.01), respectively.The area under the concentration-time curve (AUC)0-240 minutes in tears and corneas of the BTF-NM group was 7 488.90 (μg/g)·minute and 829.01 (μg/g)·minute, which was 7.2 and 52 times than that of the BTF-S group, respectively.No drugs were detected in the aqueous humor of the BTF-NM group and the BTF-S group.

Conclusions

BTF-NM is an ideal agent with a simple preparing process, high drug encapsulation efficiency and small particle size.Compared with BTF suspension, BTF-NM can significantly improve the bioavailability of BTF in rabbit corneas.

Key words:

Butenafine; Nanomicelles; Ocular pharmacokinetics; Rabbits; High-performance liquid chromatography

Contributor Information

Lu Ping
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
Liang Zhen
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou 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, Zhengzhou 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, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
Song Fei
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou 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, Zhengzhou 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, Zhengzhou 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, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou 450003, China
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Updated: December 18, 2020 — 8:06 am