Ophthalmic In Situ Gelling System Containing Lanosterol Nanoparticles Delays Collapse of Lens Structure in Shumiya Cataract Rats

We attempted to prepare ophthalmic in situ gel formulations containing lanosterol (Lan) nanoparticles (LA-NPs/ISG) and investigated the characteristics, delivery pathway into the lens, and anti-cataract effects of LA-NPs/ISG using SCR-N (rats with slight lens structure collapse) and SCR-C (rats with a combination of remarkable lens structure collapse and opacification). LA-NPs/ISG was prepared by bead milling of the dispersions containing 0.5% Lan powder, 5% 2-hydroxypropyl-β-cyclodextrin, 0.5% methylcellulose, 0.005% benzalkonium chloride, and 0.5% mannitol. The particle size distribution of Lan was 60–250 nm. The LA-NPs/ISG was gelled at 37 °C, and the LA-NPs/ISG was taken into the cornea by energy-dependent endocytosis and then released to the intraocular side. In addition, the Lan contents in the lenses of both SCR-N and SCR-C were increased by the repetitive instillation of LA-NPs/ISG (twice per day). The space and structure collapse in the lens of SCR-N with aging was attenuated by the instillation of LA-NPs/ISG. Moreover, the repetitive instillation of LA-NPs/ISG attenuated the changes in cataract-related factors (the enhancement of nitric oxide levels, calpain activity, lipid peroxidation levels, Ca(2+) contents, and the decrease of Ca(2+)-ATPase activity) in the lenses of SCR-C, and the repetitive instillation of LA-NPs/ISG delayed the onset of opacification in the SCR-C. It is possible that the LA-NPs/ISG is useful in maintaining lens homeostasis.