Planar microdevices enhance transport of large molecular weight molecules across retinal pigment epithelial cells.
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.
Department of Bioengineering and Therapeutic Sciences, University of California, 1700 4th Street, Byers Hall 204, Box 2520, San Francisco, CA, 94158, USA.
Jennifer S
JS
Wade
Tejal A
TA
Desai
D001692:Biological Transport / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000494:pharmacology; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000378:metabolism*; D004864:Equipment and Supplies; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D055616:Microtechnology; D008970:Molecular Weight; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012168:Retinal Pigments / Q000378:metabolism*; D055815:Young Adult; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D062793:Occludin; D012168:Retinal Pigments; D062826:Zonula Occludens-1 Protein; C569042:TJP1 protein, human; C015219:fluorescein isothiocyanate dextran; C421109:multidrug resistance-associated protein 1