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Shigeo Tamiya, Shunichiro Ueda, Kevin McDonald, Betty Nunn, Henry J Kaplan, Martin O'Toole; Prevention of post-traumatic proliferative vitreoretinopathy using sustained release system of dasatinib. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5814. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative vitreoretinopathy (PVR) is one of the major fibrotic complications following ocular trauma affecting the posterior segment. The purpose of this study was to examine if a sustained release system of the tyrosine kinase inhibitor dasatinib, which we have previously shown to prevent PVR associated changes both in vitro and in vivo, can prevent PVR in a large animal model of traumatic globe injury.
Dasatinib-incorportated poly(lactic-co-glycolic acid) particles (Das-PLGA) was prepared by spray drying a solution of dasatinib and PLGA dissolved in dichloromethane using Buchi B-90 Nano spray dryer. Release of dasatinib from Das-PLGA was determined by incubating Das-PLGA in PBS, and measuring dasatinib concentration in solution daily by UV absorbance. Previously established swine model of ocular trauma involving penetrating injury followed by autologous blood injection was used. Ocular examinations via indirect ophthalmoscopy and/or ultrasound were performed at 2 and 4 weeks post-operation to evaluate for PVR complications, and the effect of Das-PLGA injection was compared to injection of dasatinib solution or PLGA particles alone.
Das-PLGA demonstrated a sustained release profile of dasatinib in vitro, which was detectable up to 14 days. Majority of eyes (9 out of 11) injected with dasatinib solution or PLGA particles alone developed grade C PVR, with full thickness folds posterior to the equator. In contrast, only one eye injected with Das-PLGA developed folds and the majority of eyes (9 out of 10) had a normal retina posterior to the equator.
Das-PLGA, a slow release system for dasatinib using PLGA nanoparticles, significantly inhibited PVR development in vivo in a porcine ocular trauma model. Our data strongly implicates that a sustained release system of dasatinib can be useful in preventing traumatic PVR.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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