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Transcorneal Kinetics of Topical Drugs and Nanoparticles

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Ophthalmic Product Development

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 37))

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Abstract

Topical drugs to the eye, common among ophthalmic drugs, access the anterior chamber via corneal or noncorneal pathways with penetration across the cornea, an oil:water:oil matrix, preferred by low-molecular-weight lipophilic drugs. The kinetics of their transcorneal penetration also depends on the barrier integrity of the corneal epithelium. Over the years, we have measured time-dependent ocular surface dynamics and transcorneal kinetics of several fluorescent molecules (employed as drug surrogates) and nanoparticles using custom-built fluorometers: spot fluorometer and confocal scanning microfluorometer (CSMF), respectively. The spot fluorometer has enabled novel approaches to assess the efficacy of different vehicles for enhanced bioavailability of topical drugs. It has also quantified the variability in the ocular surface dynamics of topical drops. On the other hand, the CSMF has led to a microscopic view of the transport of fluorescent dyes across the cornea, highlighting the cellular barriers and partitioning of dyes. The data accrued from these observations have enabled rational modeling of the spatiotemporal corneal pharmacokinetics of topical drugs. Unlike the compartmental models, our models incorporate the physicochemical properties of the drugs to explain the kinetics of their penetration. In this chapter, we review our unique experimental observations and describe the framework of our pharmacokinetic model for topical drugs.

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Abbreviations

CSMF:

Confocal scanning microfluorometer

FITC:

Fluorescein isothiocyanate

Log P:

Logarithm (base 10) of octanol-water partition coefficient at pH 7.4

RhB:

Rhodamine B

SPR:

Structure permeability relationships

SRB:

Sulforhodamine B

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Authors and Affiliations

  1. Optometry, Indiana University, Bloomington, IN, USA

    Sangly P. Srinivas

  2. Optometry, Naresuan University, Phitsanulok, Thailand

    Wanachat Chaiyasan

  3. Indiana University, Bloomington, IN, USA

    Anirudh Burli

  4. Electrical Engineering, Computer Science, and Mathematics, University of Missouri, Columbia, MO, USA

    Giovanna Guidoboni

  5. Dipartimento di Matematica, Politecnico di Milano, Milan, Italy

    Riccardo Sacco

  6. Computer Science, DSCE, Bangalore, Karnataka, India

    Abhishek Anand & Amreen H. Siraj

  7. Amity Center for Nanobiotechnology and Nanomedicine, Amity Institute of Biotechnology, Amity University, Jaipur, India

    Hemant Kumar Daima

  8. Professor of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Uday B. Kompella

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  1. Sangly P. Srinivas
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  2. Wanachat Chaiyasan
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  9. Uday B. Kompella
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Correspondence to Sangly P. Srinivas .

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Editors and Affiliations

  1. Chief Operating Officer, Tarsus Pharmaceuticals Inc, Irvine, CA, USA

    Seshadri Neervannan

  2. Professor of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Uday B. Kompella

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Srinivas, S.P. et al. (2021). Transcorneal Kinetics of Topical Drugs and Nanoparticles. In: Neervannan, S., Kompella, U.B. (eds) Ophthalmic Product Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 37. Springer, Cham. https://doi.org/10.1007/978-3-030-76367-1_6

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