Influence of molecular shape, conformability, net surface charge, and tissue interaction on transscleral macromolecular diffusion

Srikantha, Nishanthan and Mourad, Fatma and Suhling, Klaus and Elsaid, Naba and Levitt, James and Chung, Pei Hua and Somavarapu, Satyanarayana and Jackson, Timothy L. (2012) Influence of molecular shape, conformability, net surface charge, and tissue interaction on transscleral macromolecular diffusion. Experimental Eye Research, 102. pp. 85-92. ISSN 00144835

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Official URL: http://doi.org/10.1016/j.exer.2012.07.007

Abstract

Purpose: To study the influence of molecular shape, conformability, net surface charge and tissue interaction on transscleral diffusion. Methods: Unfixed, porcine sclera was clamped in an Ussing chamber. Fluorophore labelled, neutral, albumin, dextran, or ficoll were placed in one hemi-chamber and the rate of transscleral diffusion was measured over 24 hours using a spectrophotometer. Experiments were repeated using dextrans and ficoll with positive, or negative, net surface charges. Fluorescence recovery after photobleaching (FRAP) was undertaken to compare transscleral diffusion with diffusion through a solution. All molecules were 70 kDa. Results: Using FRAP, mean ± SD diffusion coefficient (D) was highest for albumin, followed by ficoll, then dextran (p = 0.0005). Positive dextrans diffused fastest, followed by negative, then neutral dextrans (p = 0.0005). Neutral ficoll diffused the fastest, followed by positive then negative ficoll (p = 0.0008). For the neutral molecules, transscleral D was highest for albumin, followed by dextran, then ficoll (p < 0.0001). D was highest for negative ficoll, followed by neutral, then positive ficoll (p < 0.0001). By contrast, D was highest for positive dextran, followed by neutral, then negative dextran (p = 0.0021). Conclusions: Diffusion in free solution does not predict transscleral diffusion and the molecular-tissue interaction is important. Molecular size, shape, and charge may all markedly influence transscleral diffusion, as may conformability to a lesser degree, but all need to be considered when selecting or designing drugs for transscleral delivery.

Item Type: Journal Article
Keywords: transscleral diffusion, fluorescence recovery after photobleaching (FRAP), molecular shape, molecular conformability, diffusion, retinal disease, posterior segment drug delivery, protein delivery, ocular drug delivery
Faculty: Faculty of Medical Science
Depositing User: Dr Naba Elsaid
Date Deposited: 20 Dec 2016 08:59
Last Modified: 20 Dec 2016 08:59
URI: http://arro.anglia.ac.uk/id/eprint/701260

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