Abstract
Purpose :
CAI has been used as a systemic anti-angiogenic agent in 900+ patients with different systemic cancers. The purpose of this study was to formulate a potential sustained release safe anti-angiogenic molecule.
Methods :
A polymeric Poly lactic co-glycolic acid(PLGA)-Carboxyamidotriazole(CAI) suspension was engineered by double emulsion. To induce choroidal neovascularization, laser injury was made utilizing an Iridex laser at settings of 50µm spot, 100msec duration, and 200 mW power. The resulting choroidal neovascular membrane volume was measured by a masked examiner using bioptigen InVivoVue 2.4.34 software.
Results :
Injection of the polymeric PLGA-CAI suspension into the rabbit vitreous caused no toxicity based on retinal exam and histopathology. No inflammation or change in intraocular pressure were noted after injection. No abnormal blood chemistry or internal organ abnormalities were detected following intravitreal administration. At both 1 and 2 weeks after laser injury in mice, intravitreal injection of the PLGA-CAI polymer at a dose range from 500nM-10 µM significantly decreased choroidal neovascular volume in a dose dependent fashion. [mg1] We were able to achieve a 70% reduction in choroidal neovascular volume with this dose range. There was not a significant increase of anti-angiogenic activity observed when this dose range of PLGA-CAI was combined with intravitreal injection of 2µl of aflibercept.
Conclusions :
A stable synthetic anti-angiogenic molecule, CAI, has been formulated into a polymeric PLGA suspension. Based on manipulation of particle size and polymer composition, we speculate that PLGA-CAI can be designed to deliver either induction or sustained release therapy, thus addressing a significant unmet clinical need by reducing treatment burden of anti-angiogenic therapy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.