Characterization of Human Sclera Barrier Properties for Transscleral Delivery of Bevacizumab and Ranibizumab

The objectives of this study were to (a) investigate transscleral permeation of antivascular endothelial growth factor drugs bevacizumab and ranibizumab and (b) examine the effects of molecular structures of macromolecules upon permeation across human sclera using bevacizumab, ranibizumab, fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (FITC-BSA), FITC-labeled ficoll (FITC-ficoll), and FITC-labeled dextrans (FITC-dextrans) in vitro. The hydrodynamic radii of the macromolecules were measured using dynamic light scattering, their partition coefficients to sclera were determined in uptake experiments, and their permeability coefficients and transport lag times across sclera were evaluated in transport experiments of side-by-side diffusion cells. Macromolecules showed relatively low partition coefficients to sclera. The partition coefficient of FITC-BSA was found to be related to its concentration in the equilibration solution, whereas for other macromolecules, no specific concentration dependency was observed. The macromolecules displayed relatively low permeability coefficients and long transport lag times because of their molecular sizes and hindered diffusion. Bevacizumab, ranibizumab, and FITC-BSA exhibited lower transscleral permeability and longer transport lag times than FITC-dextrans and FITC-ficoll of comparable molecular weights possibly because of the flexible structures of the polysaccharides. Thus, the polysaccharides may not be good surrogate permeants to model transscleral transport of therapeutic proteins in transscleral delivery studies.