Nagai Noriaki, Ishii Miyu, Seiriki Ryotaro, Ogata Fumihiko, Otake Hiroko, Nakazawa Yosuke, Okamoto Norio, Kanai Kazutaka, Kawasaki Naohito
Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Pharmaceutics. 2020 Feb 14;12(2):155. doi: 10.3390/pharmaceutics12020155.
The commercially available rebamipide ophthalmic suspension (CA-REB) was approved for clinical use in patients with dry eye; however, the residence time on the ocular surface for the traditional formulations is short, since the drug is removed from the ocular surface through the nasolacrimal duct. In this study, we designed a novel sustained-release drug delivery system (DDS) for dry eye therapy by rebamipide nanoparticles. The rebamipide solid nanoparticle-based ophthalmic formulation (REB-NPs) was prepared by a bead mill using additives (2-hydroxypropyl-β-cyclodextrin and methylcellulose) and a gel base (carbopol). The rebamipide particles formed are ellipsoid, with a particle size in the range of 40-200 nm. The rebamipide in the REB-NPs applied to eyelids was delivered into the lacrimal fluid through the meibomian glands, and sustained drug release was observed in comparison with CA-REB. Moreover, the REB-NPs increased the mucin levels in the lacrimal fluid and healed tear film breakup levels in an -acetylcysteine-treated rabbit model. The information about this novel DDS route and creation of a nano-formulation can be used to design further studies aimed at therapy for dry eye.
市售瑞巴派特眼用混悬液（CA-REB）已被批准用于干眼症患者的临床治疗；然而，传统制剂在眼表的停留时间较短，因为药物会通过鼻泪管从眼表清除。在本研究中，我们设计了一种新型的瑞巴派特纳米颗粒缓释给药系统（DDS）用于干眼症治疗。采用珠磨机，使用添加剂（2-羟丙基-β-环糊精和甲基纤维素）和凝胶基质（卡波姆）制备了基于瑞巴派特固体纳米颗粒的眼用制剂（REB-NPs）。形成的瑞巴派特颗粒呈椭圆形，粒径范围为40-200nm。应用于眼睑的REB-NPs中的瑞巴派特通过睑板腺进入泪液，与CA-REB相比，观察到药物持续释放。此外，在乙酰半胱氨酸治疗的兔模型中，REB-NPs提高了泪液中的黏蛋白水平并改善了泪膜破裂情况。关于这种新型DDS途径和纳米制剂的信息可用于设计进一步的干眼症治疗研究。
