Minami Misa, Seiriki Ryotaro, Otake Hiroko, Nakazawa Yosuke, Kanai Kazutaka, Tanino Tadatoshi, Nagai Noriaki
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.
Materials (Basel). 2020 Apr 3;13(7):1675. doi: 10.3390/ma13071675.
Eye drops containing Tranilast (TL), N-(3,4-dimethoxycinnamoyl) anthramilic acid, are used as an anti-allergic conjunctivitis drug in the ophthalmic field. Traditional eye drops are very patient compliant, although the bioavailability () of most eye drops is low since eye drops cannot be instilled beyond the capacity of the conjunctival sac due to its limited volume. Thus, traditional eye drops have low and a short duration of the drug on the ocular surface, so solutions to these problems are highly anticipated. In this study, we designed a sustained-release drug-delivery system (DDS) for TL nanoparticles. TL nanoparticles were prepared by bead mill treatment, and the gel formulations containing TL nanoparticles (TL-NPs-Gel, particle size 50 nm-100 nm) were provided by carboxypolymethylene. The crystal structure of TL with and without bead mill treatment is the same, but the TL solubility in formulations containing nanoparticles was 5.3-fold higher compared with gel formulations containing TL microparticles (TL-MPs-Gel). The photo and thermal stabilities of TL-NPs-Gel are also higher than those of dissolved TL. Moreover, when TL-NPs-Gel is applied to the upper eyelid skin (outside), the TL is released as nanoparticles, and delivered to the lacrimal fluid through the meibomian glands. In addition, the TL release profile for TL-NPs-Gel was sustained over 180 min after the treatment. These findings can be used to develop a sustained-release DDS in the ophthalmic field.
含有曲尼司特（TL），即N-（3,4-二甲氧基肉桂酰基）邻氨基苯甲酸的眼药水，在眼科领域用作抗过敏性结膜炎药物。传统眼药水患者依从性很好，不过大多数眼药水的生物利用度较低，因为由于结膜囊体积有限，眼药水无法超过其容量进行滴注。因此，传统眼药水的生物利用度低，药物在眼表的作用持续时间短，所以人们迫切期待解决这些问题的方法。在本研究中，我们设计了一种用于曲尼司特纳米颗粒的缓释给药系统（DDS）。通过珠磨机处理制备曲尼司特纳米颗粒，含曲尼司特纳米颗粒的凝胶制剂（TL-NPs-Gel，粒径50nm - 100nm）由羧基聚亚甲基提供。经过和未经过珠磨机处理的曲尼司特的晶体结构相同，但与含曲尼司特微粒的凝胶制剂（TL-MPs-Gel）相比，含纳米颗粒制剂中曲尼司特的溶解度高5.3倍。TL-NPs-Gel的光稳定性和热稳定性也高于溶解态的曲尼司特。此外，当TL-NPs-Gel应用于上眼睑皮肤（外部）时，曲尼司特以纳米颗粒形式释放，并通过睑板腺输送到泪液中。另外，治疗后TL-NPs-Gel的曲尼司特释放曲线在180分钟内持续。这些发现可用于开发眼科领域中的缓释给药系统。
