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Measurement and Modeling of Diffusion Kinetics of a Lipophilic Molecule Across Rabbit Cornea

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Abstract

Purpose

To develop a kinetic model for representing the diffusion and partitioning of Rhodamine B (RhB), a fluorescent lipophilic molecule, across the cornea for gaining insights into pharmacokinetics of topical drugs to the eye.

Methods

Rabbit corneas mounted underneath a custom-built scanning microfluorometer were perfused with Ringers on both sides of the tissue. After a step change in RhB on the tear side, transients of trans-corneal fluorescence of RhB were measured at a depth resolution ∼ 8 μm.

Results

RhB distribution exhibited discontinuities at the interface between epithelium and stroma, and between stroma and endothelium. In each of the layers, fluorescence was non-uniform. Fluorescence was elevated in the epithelium and endothelium relative to the stroma. Modeling of RhB transport by diffusion in each layer and stipulation of partitioning of RhB at the cellular interfaces were required to account for trans-corneal penetration kinetics of RhB. The model parameters, estimated using the unsteady state trans-corneal RhB profiles, were found to be sensitive, and the model predicted the experimental profiles accurately.

Conclusions

Conventional pharmacokinetic models that depict cornea as a single compartment do not predict the depth-dependent kinetics of RhB penetration. The proposed model incorporates realistic transport mechanisms and thereby highlights the influence of physicochemical properties of drugs on trans-corneal kinetics.

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Acknowledgements

Supported by NIH grant R21-EY019119 and Faculty Research Grant, VP of Research, IU Bloomington, IN (SPS).

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Florida, Gainesville, Florida, USA

    Chhavi Gupta & Anuj Chauhan

  2. Department of Chemical and Biological Engineering, Drexel University, Philadelphia, Pennsylvania, 19104, USA

    Raj Mutharasan

  3. School of Optometry, Indiana University, 800 East Atwater Avenue, Bloomington, Indiana, 47405, USA

    Sangly P. Srinivas

Authors
  1. Chhavi Gupta
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  2. Anuj Chauhan
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  3. Raj Mutharasan
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  4. Sangly P. Srinivas
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Correspondence to Sangly P. Srinivas.

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Gupta, C., Chauhan, A., Mutharasan, R. et al. Measurement and Modeling of Diffusion Kinetics of a Lipophilic Molecule Across Rabbit Cornea. Pharm Res 27, 699–711 (2010). https://doi.org/10.1007/s11095-010-0066-1

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  • DOI: https://doi.org/10.1007/s11095-010-0066-1

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