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Influence of Permeant Lipophilicity on Permeation Across Human Sclera

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ABSTRACT

Purpose

The objectives of this study were to determine the effects of permeant lipophilicity on permeant uptake into and transport across human sclera for transscleral delivery.

Methods

Model permeants with a wide range of lipophilicities were selected and studied with human sclera. Uptake experiments were carried out to measure permeant partitioning into the sclera. Transport experiments were performed in side-by-side diffusion cells, and the permeability coefficients and transport lag times of the permeants across the sclera were evaluated.

Results

Permeants with higher lipophilicity showed higher partition coefficients to human sclera, and the apparent transport lag time also increased significantly as the permeant lipophilicity increased. No correlation between the permeability coefficients and lipophilicity of the model permeants was observed in this study with human sclera. A hypothesis on the different findings between the present and previous studies was proposed.

Conclusions

Permeants with higher lipophilicity exhibited stronger binding to human sclera and would therefore lead to larger permeant partitioning to the sclera and longer transport lag time. The steady-state permeability coefficients of the permeants were not significantly affected by permeant lipophilicity.

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ACKNOWLEDGEMENTS

This research was supported by NIH grant EY 015181. The authors acknowledge the use of tissues procured by the National Disease Research Interchange (NDRI) with support from NIH grant 5 U42 RR006042. The authors also thank Dr. Paul Bernstein and Moran Eye Center at the University of Utah for generously supplying us with some of the sclera tissues used in this study and Poonam Chopra for providing the transscleral transport data of tetraethylammonium, salicylate, and mannitol.

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Authors and Affiliations

  1. Division of Pharmaceutical Sciences James L. Winkle College of Pharmacy, University of Cincinnati, 3225 Eden Avenue 136 HPB, Cincinnati, Ohio, 45267, USA

    He Wen, Jinsong Hao & S. Kevin Li

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  1. He Wen
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  2. Jinsong Hao
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  3. S. Kevin Li
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Correspondence to Jinsong Hao.

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Wen, H., Hao, J. & Li, S.K. Influence of Permeant Lipophilicity on Permeation Across Human Sclera. Pharm Res 27, 2446–2456 (2010). https://doi.org/10.1007/s11095-010-0237-0

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  • DOI: https://doi.org/10.1007/s11095-010-0237-0

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