Efficient Intraocular Penetration of Topical Anti-TNF-α Single-Chain Antibody (ESBA105) to Anterior and Posterior Segment without Penetration Enhancer

PURPOSE. This study was designed to characterize ocular penetration pathways of ESBA105, a topically administered single-chain antibody (scFv) against tumor necrosis factor (TNF)-alpha, to the anterior and posterior segment of the eye. METHODS. Fresh enucleated whole eyes and isolated corneas of rabbits mounted in perfusion chambers were used for ex vivo penetration studies. In vivo pharmacokinetics and ocular biodistribution of ESBA105 after intravitreal injection or topical administration as eye drops were investigated in rabbits. RESULTS. After topical administration as eye drops, without a penetration enhancer, ESBA105 reached therapeutic levels in the anterior and posterior segment of the eye. ESBA105 migrated to aqueous humor via corneal penetration and vitreous and retina via intrascleral penetration pathways. In vivo, ESBA105 had a significantly prolonged elimination half-life in the vitreous of 25 hours compared with its serum half-life of 7 hours after i.v. administration. Therefore, based on frequency of topical dosing, a buildup of ESBA105 to distinct steady state levels in the vitreous could be achieved. CONCLUSIONS. Topically administered ESBA105 quickly reaches therapeutic levels in the anterior and posterior segment without any need for a penetration enhancer. Drug penetration and ocular biodistribution patterns of ESBA105 applied as eye drops appear highly attractive for clinical use to treat TNF-alpha dependant diseases of the eye. (Invest Ophthalmol Vis Sci. 2009;50:779-786) DOI:10.1167/iovs.08-2372