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Viral Kansara, Leroy Muya, Cherry Wan, Shelley Hancock, Thomas A Ciulla; Targeting, Compartmentalization and Durability of Suprachoroidally Injected Small Molecule Suspensions in Multiple Preclinical Models. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4168 – F0160.
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© ARVO (1962-2015); The Authors (2016-present)
To assess targeting, compartmentalization, and durability potential of suprachoroidal injection of small molecules via microneedle in multiple preclinical models and multiple drug candidates.
Suprachoroidal injection of multiple small molecule drug candidates (tyrosine kinase inhibitor (TKI), complement factor inhibitor, steroid, kallikrein inhibitor) via a proprietary microneedle were performed in multiple preclinical species (rabbit, porcine, monkey and dogs) to evaluate safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and/or bioavailability in posterior segment ocular tissues including the macula region. Multimodal imaging methods were employed ex vivo and in vivo to evaluate delivery efficiency, flow dynamics, and spread of injectate in the suprachoroidal space (SCS).
Suprachoroidal injections via proprietary microneedle customized for each species were successfully employed in multiple animal models and well-tolerated across species and multiple disease models. In total, over 1000 injections have been performed with free needle lengths between 300 and 1100 µm dependent on species-specific ocular anatomy characteristics. Injections into the SCS demonstrated circumferential and posterior spread of injectate immediately following the injection, confirmed in ex vivo porcine models. In multiple in vivo rabbit studies, an opening of the SCS in the posterior segment was observed. Suprachoroidal delivery of small molecule suspensions exhibited compartmentalization of a dose depot into posterior tissues with high drug levels in the chorioretina, including therapeutic drug levels as far as posteriorly to the optic nerve. In contrast, drug levels in the aqueous humor were 3-5 log orders lower, and negligible systemic drug exposure was observed. Ocular PK studies in rabbits and monkeys showed durability of multiple drug candidates. Specifically, one small molecule drug candidate showed sustained presence at 6 months (last time point evaluated). Suprachoroidally injected steroid and TKI drug candidates exhibited PD effects in in vivo porcine models of ocular inflammation and neovascularization, respectively.
Suprachoroidally injected small molecule suspensions consistently exhibit targeting, compartmentalization, and durability in multiple preclinical models.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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