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Related Experiment Video

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Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
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Topical Solution for Retinal Delivery: Bevacizumab and Ranibizumab Eye Drops in Anti-Aggregation Formula (AAF) in

Steven A Giannos1, Edward R Kraft2, Jonathan D Luisi2

  • 1Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX, USA. stevena.giannos@viatris.com.

Pharmaceutical Research
|June 5, 2024
PubMed
Summary

Topical eye drops with a novel anti-aggregation formula (AAF) successfully delivered bevacizumab and ranibizumab to the retina in rabbits. This topical delivery method shows potential as an adjunct to standard intravitreal injections for retinal diseases.

Keywords:
anti-VEGFantibodymacular degenerationneovascularizationretina

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Area of Science:

  • Ophthalmology
  • Retinal Diseases
  • Drug Delivery

Background:

  • Wet age-related macular degeneration (AMD) is a leading cause of blindness.
  • Current standard treatments involve monthly intravitreal injections of anti-VEGF antibodies like bevacizumab and ranibizumab.
  • Antibody aggregation can hinder ocular absorption and distribution, potentially limiting treatment efficacy.

Purpose of the Study:

  • To assess the topical delivery of dilute anti-VEGF antibodies (bevacizumab and ranibizumab) to the posterior segment of rabbit eyes.
  • To evaluate the efficacy of a novel anti-aggregation formula (AAF) in enhancing ocular absorption and distribution of these antibodies.
  • To determine if topical delivery can achieve therapeutic concentrations in retinal tissues.

Main Methods:

  • Bevacizumab or a ranibizumab biosimilar were diluted in AAF to 5 mg/ml.
  • Rabbits received twice-daily topical eye drops (100 µl for bevacizumab, 50 µl for ranibizumab biosimilar).
  • Ocular and serum samples were collected and analyzed for antibody concentrations using AAF as a diluent.

Main Results:

  • Bevacizumab in AAF showed 10 times greater permeation and accumulation in rabbit aqueous, vitreous, and retina compared to PBS.
  • Twice-daily dosing of AAF/hyaluronic acid eye drops achieved significant retinal concentrations (29.50 ng/g for bevacizumab, 18.0 ng/g for ranibizumab biosimilar).
  • Minimal serum concentrations were detected, and no ocular irritation was observed.

Conclusions:

  • Topical delivery of bevacizumab and ranibizumab using an AAF diluent eye drop formulation is feasible.
  • This method allows for effective delivery of monoclonal antibodies to the retina.
  • Topical anti-VEGF eye drops may serve as a valuable adjunct to intravitreal injections for managing retinal diseases.