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羊毛甾醇与尼伐地平纳米混悬液联合用药可缓解亚硒酸盐诱导的白内障大鼠的晶状体混浊

Combination of Lanosterol and Nilvadipine Nanosuspensions Rescues Lens Opacification in Selenite-Induced Cataractic Rats.

作者信息

Deguchi Saori, Kadowaki Reita, Otake Hiroko, Taga Atsushi, Nakazawa Yosuke, Misra Manju, Yamamoto Naoki, Sasaki Hiroshi, Nagai Noriaki

机构信息

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

Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku 105-8512, Tokyo, Japan.

出版信息

Pharmaceutics. 2022 Jul 21;14(7):1520. doi: 10.3390/pharmaceutics14071520.

DOI:10.3390/pharmaceutics14071520
PMID:35890415
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9318002/
Abstract

It has recently been reported that lanosterol (LAN) plays a preventive role against lens opacification through the reversal of crystalline aggregation. However, the effect of LAN is not sufficient to restore lens transparency. In this study, we designed ophthalmic nanosuspensions (LAN-ONSs and NIL-ONSs) based on LAN and nilvadipine (NIL), which can counteract cataract-related factors (e.g., enhanced Ca and calpain levels), and investigated whether the combination of LAN-ONSs and NIL-ONSs can restore the nuclear lens opacity in sodium-selenite-induced cataractic rats (cataractic rats). The mean particle sizes of the LAN-ONSs and NIL-ONSs were 108.8 nm and 89.0 nm, respectively. The instillation of the LAN-ONSs or NIL-ONSs successfully delivered the drugs (LAN or NIL) into the lenses of the rats, although the instillation of LAN-ONSs or NIL-ONSs alone did not increase lens transparency in the cataractic rats. On the other hand, the cataract-related factors (enhanced Ca and calpain levels) were significantly alleviated by the combination of LAN-ONSs and NIL-ONSs; furthermore, the perinuclear refractile ring in the lens nucleus and enhanced number of swollen fibers were attenuated by the LAN-ONS and NIL-ONS combination. Moreover, the opacity levels in the cataractic rats were reduced after treatment with the combination of LAN-ONSs and NIL-ONSs. It is possible that the combination of LAN and NIL will be useful for the treatment of lens opacification in the future.

摘要

最近有报道称，羊毛甾醇（LAN）通过逆转晶状体蛋白聚集对晶状体混浊起到预防作用。然而，LAN的效果不足以恢复晶状体透明度。在本研究中，我们基于LAN和尼伐地平（NIL）设计了眼科纳米混悬剂（LAN - ONSs和NIL - ONSs），它们可以对抗白内障相关因素（如钙和钙蛋白酶水平升高），并研究LAN - ONSs和NIL - ONSs的组合是否能恢复亚硒酸钠诱导的白内障大鼠（白内障大鼠）的晶状体核混浊。LAN - ONSs和NIL - ONSs的平均粒径分别为108.8 nm和89.0 nm。LAN - ONSs或NIL - ONSs的滴眼成功地将药物（LAN或NIL）递送至大鼠晶状体中，尽管单独滴眼LAN - ONSs或NIL - ONSs并未增加白内障大鼠的晶状体透明度。另一方面，LAN - ONSs和NIL - ONSs的组合显著减轻了白内障相关因素（钙和钙蛋白酶水平升高）；此外，LAN - ONS和NIL - ONS组合减轻了晶状体核中的核周折光环和肿胀纤维数量的增加。此外，LAN - ONSs和NIL - ONSs组合治疗后，白内障大鼠的混浊程度降低。LAN和NIL的组合未来可能对治疗晶状体混浊有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/1f59f1cbde2f/pharmaceutics-14-01520-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/0748395234fe/pharmaceutics-14-01520-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/82414dded9bf/pharmaceutics-14-01520-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/0cfd4e64b1c4/pharmaceutics-14-01520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/f29e67ff6d12/pharmaceutics-14-01520-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/1f59f1cbde2f/pharmaceutics-14-01520-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/0748395234fe/pharmaceutics-14-01520-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/c4eb640dafd4/pharmaceutics-14-01520-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/ba818a63eb1a/pharmaceutics-14-01520-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/0acabe861bb7/pharmaceutics-14-01520-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/82414dded9bf/pharmaceutics-14-01520-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/0cfd4e64b1c4/pharmaceutics-14-01520-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/f29e67ff6d12/pharmaceutics-14-01520-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a730/9318002/1f59f1cbde2f/pharmaceutics-14-01520-g008.jpg

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