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含有羊毛甾醇纳米颗粒的眼用原位凝胶系统延缓了舒米亚白内障大鼠晶状体结构的塌陷。

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

作者信息

Nagai Noriaki, Umachi Kazuki, Otake Hiroko, Oka Mikako, Hiramatsu Noriko, Sasaki Hiroshi, Yamamoto Naoki

机构信息

Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.

Laboratory of Clinical Pharmacology, Yokohama University of Pharmacy, Yokohama, Kanagawa 245-0066, Japan.

出版信息

Pharmaceutics. 2020 Jul 4;12(7):629. doi: 10.3390/pharmaceutics12070629.

DOI:10.3390/pharmaceutics12070629
PMID:32635523
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7408553/
Abstract

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 contents, and the decrease of Ca-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.

摘要

我们试图制备含有羊毛甾醇（Lan）纳米颗粒的眼用原位凝胶制剂（LA-NPs/ISG），并使用SCR-N（晶状体结构轻度塌陷的大鼠）和SCR-C（晶状体结构显著塌陷并伴有混浊的大鼠）研究LA-NPs/ISG的特性、进入晶状体的递送途径以及抗白内障作用。通过对含有0.5% Lan粉末、5% 2-羟丙基-β-环糊精、0.5%甲基纤维素、0.005%苯扎氯铵和0.5%甘露醇的分散体进行珠磨来制备LA-NPs/ISG。Lan的粒径分布为60-250 nm。LA-NPs/ISG在37℃时凝胶化，LA-NPs/ISG通过能量依赖性内吞作用进入角膜，然后释放到眼内一侧。此外，通过每天两次重复滴注LA-NPs/ISG，SCR-N和SCR-C晶状体中的Lan含量均增加。滴注LA-NPs/ISG可减轻SCR-N晶状体随年龄增长出现的空间和结构塌陷。此外，重复滴注LA-NPs/ISG可减轻SCR-C晶状体中与白内障相关因素的变化（一氧化氮水平升高、钙蛋白酶活性、脂质过氧化水平、钙含量增加以及钙-ATP酶活性降低），并且重复滴注LA-NPs/ISG可延缓SCR-C晶状体混浊的发生。LA-NPs/ISG可能有助于维持晶状体的内环境稳定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/5de0743d1b2a/pharmaceutics-12-00629-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/cd37804fa532/pharmaceutics-12-00629-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/76f4e713f46f/pharmaceutics-12-00629-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/331e5c630005/pharmaceutics-12-00629-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/daa8500f0860/pharmaceutics-12-00629-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/b943254c14ad/pharmaceutics-12-00629-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/5de0743d1b2a/pharmaceutics-12-00629-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/cd37804fa532/pharmaceutics-12-00629-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/1a1ad7d997fc/pharmaceutics-12-00629-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/76f4e713f46f/pharmaceutics-12-00629-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/331e5c630005/pharmaceutics-12-00629-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/daa8500f0860/pharmaceutics-12-00629-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/b943254c14ad/pharmaceutics-12-00629-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/7408553/5de0743d1b2a/pharmaceutics-12-00629-g007.jpg

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