Abstract
Purpose :
Wet AMD is a disastrous disease of vision loss where the only medicinal treatment currently available is an intraocular injection of aflibercept or ranibizumab. However, such an intravitreal injection often causes various side-effects and complication. Therefore, we prepared and evaluated eyedrops of three VEGFR tyrosine kinase inhibitors (TKIs) for a safer, non-invasive solution of wet AMD.
Methods :
Three TKIs — sunitinib, pazopanib, and axitinib — are aqueously dispersed with our proprietary technology: D-SUT (0.05%), D-PZP (0.2%), and D-AXT (0.01%). C57BL/6 mice were used for a laser-induced choroidal neovascularization (CNV) model. A total of 30 mice were classified into six groups: G1 (PBS), G2 (aflibercept), G3 (SUT solution, 0.05%), G4(D-SUT), G5 (D-PZP), G6 (D-AXT). Aflibercept (1 uL/eye) was given as single intravitreal injection. Test samples and PBS (5 uL/eye each) were instilled twice a day for 10 days. Corrected total fluorescence and volume of CNV lesions were measured after 10 treatment days by FFA and OCT, respectively. The concentration of test samples at the retina was measured.
Results :
D-SUT, D-PZP and D-AXT, given as eyedrops, showed statistically significant suppression of the CNV lesion volume by 49%, 26%, and 25%, respectively, compared to the PBS control (p<0.0001, p<0.01, and p<0.05, respectively), whereas SUT solution itself did not. The efficacy of D-SUT is statistically significant compared to that of SUT (p<0.05) as well. All three TKI dispersions showed comparable suppression of the area and volume of CNV lesion with the aflibercept injection. Given the concentrations of TKIs in the retina, sufficient amounts of TKIs were delivered to the retina.
Conclusions :
We have demonstrated that the eyedrops of three TKI dispersions showed comparable efficacy with the intravitreal injection of aflibercept. Corresponding ocular pharmacokinetic study and tissue distribution analysis of TKI dispersion support the straightforward way of drug delivery through the cornea to the retina. Further efforts to develop the TKI eyedrops for patient-friendly wet AMD treatments are under way.
This is a 2021 ARVO Annual Meeting abstract.