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Carboxyamidotriazole Complexed to PLGA Is Safe, Effective, and Durable in Models of Neovascular Retinal Disease

  • 0Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Translational Vision Science & Technology +

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March 25, 2025

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March 25, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Carboxyamidotriazole (CAI) nanoparticles and implants effectively reduced choroidal neovascularization and vascular leakage in preclinical models. This anti-angiogenic therapy demonstrated potent efficacy and long-term durability without observed retinal toxicity.

Area Of Science

  • Ophthalmology
  • Nanomedicine
  • Angiogenesis Inhibition

Background

  • Choroidal neovascularization (CNV) and vascular leakage are key drivers of vision loss.
  • Developing sustained-release anti-angiogenic therapies is crucial for managing these conditions.
  • Carboxyamidotriazole (CAI) is a potential therapeutic agent for neovascular eye diseases.

Purpose Of The Study

  • To evaluate the safety and bioactivity of carboxyamidotriazole (CAI) using nanoparticle and intravitreal implant formulations.
  • To assess CAI's efficacy in preclinical models of choroidal neovascularization (CNV) and vascular leakage.
  • To compare CAI's performance against aflibercept, a standard anti-VEGF therapy.

Main Methods

  • Laser-induced CNV in mice and vascular leakage model in rabbits were utilized.
  • CAI was administered as a polymeric nanoemulsion (CAI-PLGA) and a bioresorbable intravitreal implant.
  • Efficacy was assessed using fundus imaging and vitreous fluorophotometry; safety was evaluated by monitoring for toxicity.

Main Results

  • CAI nanoparticles significantly reduced choroidal neovascular volume in mice, comparable to aflibercept.
  • CAI intravitreal implants demonstrated sustained reduction in vascular leakage and neovascularization in rabbits.
  • No retinal toxicity was observed in any treatment group across both models.

Conclusions

  • CAI, in both nanoparticle and sustained-release implant forms, exhibits potent anti-angiogenic efficacy.
  • CAI demonstrates significant potential as a long-lasting, safe therapy for neovascular eye diseases.
  • Sustained release of CAI offers a promising approach for durable anti-angiogenic treatment.