Anglia Ruskin University

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

journal contribution
posted on 2023-07-26, 14:00 authored by Nishanthan Srikantha, Fatma Mourad, Klaus Suhling, Naba Elsaid, James Levitt, Pei Hua Chung, Satyanarayana Somavarapu, Timothy L. Jackson
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.



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Experimental Eye Research






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ARCHIVED Faculty of Medical Science (until September 2018)