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In vitro and ex vivo corneal penetration and absorption models

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Abstract

Topical drug administration is the preferred route of drug delivery to the eye despite the poor bioavailability. To develop more efficient drug carriers, reliable in vitro or ex vivo models are required in the early stages of formulation development, with such methods being faster, cheaper, and more ethical alternatives to in vivo studies. In vitro cell culture models are increasingly being used for transcorneal penetration studies, with primary cell cultures and immortalized cell lines now giving way to the development of organotypic corneal constructs for studying ocular drug bioavailability. Artificially cultured human corneal equivalents are still in the early stages of development, but present tremendous potential for corneal penetration studies. Ex vivo models using excised animal tissue are also being used to study corneal penetration with promising results, although significant inter-species variations need to be considered. This review discusses the in vitro and ex vivo models currently being used to study corneal penetration and evaluates their advantages and limitations with a focus on diffusion cell assemblies. In addition to the tissue used, the diffusion cell set-up can significantly influence the penetration profile and should be cautiously adjusted to simulate clinical conditions.

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Abbreviations

HCE:

Human corneal epithelial cells

TEER:

Transepithelial electrical resistance

p-HCl:

Pilocarpine hydrochloride

HCE-T:

Transformed human corneal epithelial cells

SIRC:

Statens Serum Institut rabbit corneal cells

S-HCE:

SkinEthic human corneal epithelium

C-HCE:

Clonetics human corneal epithelium

HCC:

Human corneal construct

CsA:

Cyclosporine A

GBR:

Glutathione bicarbonate ringer

PBS:

Phosphate-buffered saline

BSS:

Balanced salt solution

HEPES:

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

SLNs:

Solid lipid nanoparticles

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Acknowledgements

The authors would like to thank Novaliq GmbH, Germany, for their financial support in the form of a scholarship to Priyanka Agarwal.

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  1. Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    Priyanka Agarwal & Ilva D. Rupenthal

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  1. Priyanka Agarwal
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  2. Ilva D. Rupenthal
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Correspondence to Ilva D. Rupenthal.

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Agarwal, P., Rupenthal, I.D. In vitro and ex vivo corneal penetration and absorption models. Drug Deliv. and Transl. Res. 6, 634–647 (2016). https://doi.org/10.1007/s13346-015-0275-6

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