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S. Nicoli, G. Ferrari, S. Pescina, C. Macaluso, P. Santi; Transscleral Permeation of Bevacizumab: Effect of Iontophoresis Application. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5162.
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© ARVO (1962-2015); The Authors (2016-present)
Bevacizumab (Avastin) is an anti-VEGF monoclonal antibody that has demonstrated substantial efficacy, when administered by repeated intravitreal injection, in the treatment of common and sight threatening conditions such as neovascular age-related macular degeneration (wet-AMD) and diabetic retinopathy. The purpose of this work was to evaluate in vitro the effect of iontophoresis on the transscleral transport of bevacizumab, in view of a non-invasive administration of this drug
Bevacizumab fluorescently labelled using fluorescein isotiocianate (FITC). Permeation experiments were conducted for 2 hours in Franz-type diffusion cells using human sclera as barrier. The donor compartment contained FITC-bevacizumab (2.5 mg/ml) in PBS at pH 7.4. The receptor solution was pH 7.4 PBS termostatted at 37°C and magnetically stirred. In the current-assisted experiments, a current intensity of 2.3 mA (current density: 3.8 mA/cm2) was applied using salt bridges. Both cathodal and anodal iontophoresis were tested. The permeation samples were analysed with a fluorescence detector; the excitation and emission were 490 and 520 respectively. The stability of the FITC-bevacizumab conjugate after current application was checked by TLC.
The FITC/bevacizumab ratio after derivatization resulted approximately 0.5. The obtained conjugate was stable to current application. Bevacizumab was able to passively cross human sclera in-vitro: the transscleral flux obtained was 3.04± 0.2 µgcm-2h-1 (permeability coefficient P=3.3±0.23 *10-7 cm s-1). When cathodal iontophoresis was applied, the flux did not change, while with anodal iontophoresis the transscleral flux raised to 38.8 ± 0.8 µgcm-2h-1 (P=42.1± 0.82 *10-7 cm s-1). The amount of bevacizumab permeated after two hours of anodal iontophoresis resulted 10 fold higher than after passive diffusion.
Preliminary results indicates that anodal iontophoresis could be a promising strategy to non-invasively deliver bevacizumab through the sclera for the treatment of the posterior segment eye diseases.
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