Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5394_Библиотеки_им_академика_М_И_Перельмана

Until recently, there was little information around the ability of proteins to transit to the back of the eye via topical eye drops. Molecules as large as dextran (70 kDa) have been demonstrated to penetrate the sclera, the permeability of which has been shown to be inversely correlated with the radius of the molecule (Ambati et al. 2000; Geroski and Edelhauser 2001). Overall, there is little barrier to the diffusion of small and large molecules across the scleral meshwork from extra-scleral periocular fluid. An engineered 28 kDa single chain variable-region fragment (scFv) was shown to yield, via eye drop administration (50 mL; 0.2 mg/mL; application every 20 min for 12 h), ~3 mg/mL of antibody in the aqueous humor of rabbit eyes (Thiel et al. 2002). In contrast, a full-length 146 kDa IgG antibody, was not detected in this compartment. Levels in posterior tissues were not reported. However, in a subse­quent report by the same investigator (Williams et al. 2005), it was shown that anti­body fragments can be delivered to the back of the eye. Topical dosing of an eye drop formulation of the 28 kDa scFv (50 mL; 0.2 mg/mL; application every 20 min for 12 h) yielded vitreous drug levels of 50–150 ng/mL at 12 h post dosing. Under the same protocol, the full-length IgG was not detected in vitreous, and indicates that higher molecular weight proteins may not penetrate to posterior tissues. In Dutch-Belted rabbits, antibody was not detected in the serum, suggesting a local path for drug transit to back of eye.