Permeability of the Retina and RPE-Choroid-Sclera to Three Ophthalmic Drugs and the Associated Factors.

Hyeong Min Kim,Hye Kyoung Hong,Ji Hyun Park,Hyuncheol Kim,Kyu Hyung Park,Hyounkoo Han,Se Joon Woo

doi:10.3390/pharmaceutics13050655

Hyeong Min Kim, Hye Kyoung Hong + Show 5 more

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https://doi.org/10.3390/pharmaceutics13050655

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Abstract

In this study, Retina-RPE-Choroid-Sclera (RCS) and RPE-Choroid-Sclera (CS) were prepared by scraping them off neural retina, and using the Ussing chamber we measured the average time–concentration values in the acceptor chamber across five isolated rabbit tissues for each drug molecule. We determined the outward direction permeability of the RCS and CS and calculated the neural retina permeability. The permeability coefficients of RCS and CS were as follows: ganciclovir, 13.78 ± 5.82 and 23.22 ± 9.74; brimonidine, 15.34 ± 7.64 and 31.56 ± 12.46; bevacizumab, 0.0136 ± 0.0059 and 0.0612 ± 0.0264 (×10−6 cm/s). The calculated permeability coefficients of the neural retina were as follows: ganciclovir, 33.89 ± 12.64; brimonidine, 29.83 ± 11.58; bevacizumab, 0.0205 ± 0.0074 (×10−6 cm/s). Between brimonidine and ganciclovir, lipophilic brimonidine presented better RCS and CS permeability, whereas ganciclovir showed better calculated neural retinal permeability. The large molecular weight drug bevacizumab demonstrated a much lower permeability than brimonidine and ganciclovir. In conclusion, the ophthalmic drug permeability of RCS and CS is affected by the molecular weight and lipophilicity, and influences the intravitreal half-life.

Highlights

Regarding the elimination/clearance process, retinal pigment epithelium (RPE) is considered as a major barrier in the posterior segment ocular delivery, which is located between the neural retina and choroid [1,6]
These are eliminated via the anterior and posterior pathways across the blood-ocular barriers, including the blood-aqueous barrier (BAB) and blood-retinal barrier (BRB), which consists of the retinal pigment epithelium (RPE) and endothelium of the retinal vessels [7,8,9]
The purpose of our study was to provide systematic data on the pre-clinically measured permeability coefficients in posterior segment tissues, and to help clinicians and researchers to assess the intraocular pharmacokinetics of three substantial drug compounds being investigated and engineered for the advancement of ocular drug delivery systems

Summary

Introduction

Regarding the elimination/clearance process, retinal pigment epithelium (RPE) is considered as a major barrier in the posterior segment ocular delivery, which is located between the neural retina and choroid [1,6]. After intravitreal injection of newly developed anti-vascular endothelial growth factor (VEGF) drugs or small molecular drugs, the molecules diffuse in the intraocular space. These are eliminated via the anterior (aqueous humor) and posterior (retina-RPE-choroid) pathways across the blood-ocular barriers, including the blood-aqueous barrier (BAB) and blood-retinal barrier (BRB), which consists of the retinal pigment epithelium (RPE) and endothelium of the retinal vessels [7,8,9]. Drug permeability in the posterior segment, the neural retina, RPE, and choroid, is important to achieve better drug efficacy

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