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

• Main Authors: Noriaki Nagai, Kazuki Umachi, Hiroko Otake, Mikako Oka, Noriko Hiramatsu, Hiroshi Sasaki, Naoki Yamamoto
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Pharmaceutics
• Subjects: nanoparticles; lanosterol; cataract; in situ gel; Shumiya cataract rat
• Online Access: https://www.mdpi.com/1999-4923/12/7/629

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, Ca²⁺ contents, and the decrease of Ca²⁺-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.