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Brian Burke, Samirkumar Rajnikant Patel, Donna Taraborelli, Craig B Struble, Glenn Noronha; Targeted delivery of triamcinolone acetonide and CLS011A to the posterior ocular tissues via suprachoroidal administration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4112.
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© ARVO (1962-2015); The Authors (2016-present)
Data for the ocular distribution of two drugs, triamcinolone acetonide (TA, corticosteroid) and CLS011A (tyrosine kinase inhibitor) following suprachoroidal administration in rabbit eyes, will be presented.
Suprachoroidal and intravitreal administration of TA (40 mg/mL) was performed bilaterally into rabbit eyes. An additional group of animals were injected with a proprietary aqueous suspension of CLS011A (40 mg/mL) into the suprachoroidal space (SCS). Animals (n=2/time point) were sacrificed on at least 5 time points within 91 days. Ocular tissues (sclera/choroid/retinal pigment epithelium: SCR, retina, vitreous, iris-ciliary body: ICB, aqueous, and lens) and plasma were collected for quantification of drug concentrations. Analyses were performed using high performance liquid chromatography assays.
TA was detectable throughout the 91 day period in eyes dosed by either suprachoroidal or intravitreal administration. Based on area under the curve analysis, 96% of the drug was exposed to SCR and retina after SCS administration, in comparison to 20% in these tissues following intravitreal administration (IVT). Retinal exposure was similar between the two groups: 19% SCS vs 15% IVT. A large difference was seen in the ICB exposure: <1% SCS vs 25% IVT. Results from suprachoroidal CLS011A showed drug levels in the SCR that were at least 3 orders of magnitude higher than vitreous and drug was below limits of detection (1 ng/mL) in the aqueous. These relative distribution levels for each drug were maintained during the 3 month study period.
Suprachoroidal administration of TA and CLS011A were targeted to the SCR and retina and targeting was maintained over 3 months. These data might have implications for a better therapeutic and/or safety profile for the treatment of chorio-retinal diseases.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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