Absorption and distribution characteristics of terbinafine hydrochloride nanoemulsions in cornea after instillation

Authors: Zhou Tianyang,  Xia Huiyun,  He Jijun,  Liu Susu,  He Siyu,  Zhang Junjie
DOI: 10.3760/cma.j.issn.2095-0160.2015.10.010
Published 2015-10-10
Cite as Chin J Exp Ophthalmol, 2015,33(10): 910-914.

Abstract                            [Download PDF] [Read Full Text]

Background

Nanoemulsions (NEs) is one of the most popular ophthalmic colloidal drug delivery system due to its long-term stability, low toxicity and irritancy, considerable capacity for solubilization of lipophilic drug molecules and great potential in bioavailability improvement.The cornea pathway is the main route of intraocular absorption after topical use of NEs.Though NEs possess numerous physiological and physicochemical advantages, the use of NEs cannot always obtain satisfactory results.

Objective

This study was to investigate the impacts of epithelium and stroma on the corneal permeation of topical ophthalmic terbinafine hydrochloride nanoemulsions (TH-NEs).

Methods

TH-NEs was prepared by the self-emulsification method.The size and Zeta potential of the oil droplets in the formulation were analyzed using a dynamic light-scattering particle size analyzer.The high performance liquid chromatography (HPLC) was used for the in vitro release study.Sixty New Zealand albino rabbits were randomly divided into intact cornea group and cornea epithelium debrided group.The cornea epithelium of the left eyes was debrided in the cornea epithelium debrided group.The TH-NEs were instilled into the lower conjunctival sac of left eyes.Six rabbits were executed from each group 15, 30, 60, 120 and 240 minutes after dosing, respectively.The corneas were collected and analyzed by HPLC.The fluorescein diacetate (FDA) was used to label the TH-NEs.Two C57BL/6 mice with left cornea epithelium debrided and 2 normal mice were used for the fluorescence tracing study.The fluorescence distribution of FDA labeled TH-NEs was observed by a two-photon laser confocal scanning microscope 30 minutes and 60 minutes after single instillation.

Results

The average size and Zeta potential of the oil droplets were 51.37 nm and -0.232 7 mV respectively, and 0.482% of encapsulated drugs was released from the TH-NEs after 12 hours.The peak concentrations of TH in the intact cornea and epithelium debrided cornea were (17.85±2.79)μg/g and (4.40±1.75)μg/g respectively, which occurred 15 minutes post-dose.The drug concentrations in the intact cornea were significantly higher than that in the debrided cornea 15, 30, 60 and 120 minutes after dosing, with significant differences between them (t=9.998, 8.658, 6.903, 7.576; all at P=0.000). The fluorescence was observed in the cornea epithelium when the cornea was intact.The fluorescence intensity in the superior layer of corneal epithelium was obviously higher than that in the deep layers of corneal epithelium 30 minutes and 60 minutes after dosing.No fluorescence was observed in the cornea stroma of both eyes.

Conclusions

The cornea epithelium is the main of absorption and distribution position of TH-NEs.The cornea stroma is the dominating permeation barrier for the intraocular transportation of the TH-NEs.The cornea stroma may stop the permeation of TH-NEs by molecular exclusion mechanism.

Key words:

Terbinafine hydrochloride; Nanoemulsions; Corneal epithelium; Corneal stroma; Tissue distribution

Contributor Information

Zhou Tianyang
Henan Eye Institute, Henan Eye Hospital, Zhengzhou 450003, China
Xia Huiyun
He Jijun
Liu Susu
He Siyu
Zhang Junjie
(Read 48 times, 1 visits today)
Updated: March 1, 2023 — 2:48 am