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Planar microdevices enhance transport of large molecular weight molecules across retinal pigment epithelial cells

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Abstract

Large molecular weight drug delivery to the posterior eye is challenging due to cellular barriers that hinder drug transport. Understanding how to enhance transport across the retinal barrier is important for the design of new drug delivery systems. A novel mechanism to enhance drug transport is the use of geometric properties, which has not been extensively explored in the retina. Planar SU-8/Poly(ethyleneglycol)dimethacrylate microdevices were constructed using photolithography to deliver FITC dextran across an in vitro retinal model. The model consists of retinal pigment epithelial (RPE) cells grown to confluence on transwell inserts, which provides an environment to investigate the influence of geometry on paracellular and transcellular delivery of encapsulated large molecules. Planar microdevices enhanced transport of large molecular weight dextrans across different models of RPE in a size dependent fashion. Increased drug permeation across the RPE was observed with the addition of microdevices as compared to a traditional bolus of FITC dextran. This phenomena was initiated by a non-toxic interaction between the microdevices and the retinal tight junction proteins. Suggesting that increased drug transport occurs via a paracellular pathway. These experiments provide evidence to support the future use of planar unidirectional microdevices for delivery of biologics in ocular applications.

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Acknowledgments

Funding to conduct this research was generously provided by Genentech, Inc and the National Institutes of Health (NIH). The hfRPE cells were generously provided by the laboratory of Dr. Sheldon Miller at the National Eye Institute (NEI). The author is grateful for the guidance on hfRPE cultivation provided by Dr. Arvydas Maminishkis of the Miller laboratory. All microfabrication work was performed in the UCSF Micro and Nanofabrication Core facility. We thank Dr. Jessica Allen, Dr. Miquella G. Chavez, Dr. Hariharasudhan D. Chirra, Dr. Osi Esue, Dr. Lalitha Muthusubramaniam and Dr. Vuk Uskokovic for their valuable insight and advice.

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Authors and Affiliations

  1. Department of Bioengineering and Therapeutic Sciences, University of California, 1700 4th Street, Byers Hall 204, Box 2520, San Francisco, CA, 94158, USA

    Jennifer S. Wade & Tejal A. Desai

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  1. Jennifer S. Wade
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  2. Tejal A. Desai
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Correspondence to Tejal A. Desai.

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Fig. S1

Planar Device SEM. Scanning electron microscopy cross-section of a single planar microdevice with an empty reservoir (EPS 15494 kb)

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Fig. S2

FITC Dextran Elution. Elution of FITC dextran from SU-8/PEGDMA planar microdevices over 10.5 h. All experiments were conducted in PBS at 37 °C. Error bars represent the mean +/−standard deviation (EPS 691 kb)

High Resolution (JPEG 202 kb)

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Wade, J.S., Desai, T.A. Planar microdevices enhance transport of large molecular weight molecules across retinal pigment epithelial cells. Biomed Microdevices 16, 629–638 (2014). https://doi.org/10.1007/s10544-014-9865-1

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