Journal article
Measurement and Modeling of Diffusion Kinetics of a Lipophilic Molecule Across Rabbit Cornea
Pharmaceutical research, v 27(4), pp 699-711
01 Apr 2010
PMID: 20182774
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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 similar to 8 mu m.
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.
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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Details
- Title
- Measurement and Modeling of Diffusion Kinetics of a Lipophilic Molecule Across Rabbit Cornea
- Creators
- Chhavi Gupta - University of FloridaAnuj Chauhan - University of FloridaRaj Mutharasan - Drexel UniversitySangly P. Srinivas - School of Optometry Indiana University Bloomington USA
- Publication Details
- Pharmaceutical research, v 27(4), pp 699-711
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- R21-EY019119 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA VP of Research, IU Bloomington, IN R21EY019119 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000275556000016
- Scopus ID
- 2-s2.0-77953163646
- Other Identifier
- 991019170973904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary
- Pharmacology & Pharmacy