Nagai Noriaki, Ogata Fumihiko, Otake Hiroko, Kawasaki Naohito, Nakazawa Yosuke, Kanai Kazutaka, Okamoto Norio, Shimomura Yoshikazu
Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Exp Eye Res. 2017 Dec;165:118-124. doi: 10.1016/j.exer.2017.10.002. Epub 2017 Oct 5.
We prepared magnesium hydroxide (MH) nanoparticles by a bead mill method, and investigated whether the co-instillation of MH nanoparticles improves the low transcorneal penetration of water-soluble drugs, such as the anti-glaucoma eye drug timolol maleate (TM). MH particle size was decreased by the bead mill treatment to a mean particle size of 71 nm. In addition, the MH nanoparticles were highly stable. Next, we demonstrated the effect of MH nanoparticles on the corneal surface. MH shows only slight solubility in lacrimal fluid, and the instillation of MH nanoparticles for 14 days did not affect the behavior (balance of secretion and excretion) of the lacrimal fluid in rabbit corneas. Moreover, there was no observable corneal toxicity of MH nanoparticles, and treatment with MH nanoparticles enhanced the intercellular space ratio in the eyes of rats. MH alone did not permeate into the cornea; however, the co-instillation of MH nanoparticles and dissolved TM (nMTFC) enhanced the corneal penetration of TM. In addition, the intraocular pressure (IOP)-reducing effect of nMTFC was significantly higher than those of the TM solution or the co-instillation of MH microparticles and TM. In conclusion, we found that MH nanoparticles enhance the corneal penetration of dissolved TM with no observable corneal stimulation or obstruction of the nasolacrimal duct by the MH nanoparticles. It is possible that the co-instillation of MH nanoparticles may provide a useful way to improve the bioavailability of water-soluble drugs in the ophthalmic field. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma eye drugs.
我们通过珠磨机法制备了氢氧化镁（MH）纳米颗粒，并研究了MH纳米颗粒的共同滴注是否能改善水溶性药物（如抗青光眼眼药马来酸噻吗洛尔（TM））的低角膜透过率。通过珠磨机处理，MH的粒径减小至平均粒径71nm。此外，MH纳米颗粒具有高度稳定性。接下来，我们证明了MH纳米颗粒对角膜表面的影响。MH在泪液中仅表现出轻微的溶解性，滴注MH纳米颗粒14天对兔角膜泪液的行为（分泌和排泄平衡）没有影响。此外，未观察到MH纳米颗粒对角膜有毒性，并且用MH纳米颗粒处理可提高大鼠眼中的细胞间隙率。单独的MH不能渗透到角膜中；然而，MH纳米颗粒与溶解的TM共同滴注（nMTFC）可增强TM的角膜透过率。此外，nMTFC降低眼内压（IOP）的效果明显高于TM溶液或MH微粒与TM共同滴注的效果。总之，我们发现MH纳米颗粒可增强溶解的TM的角膜透过率，且未观察到MH纳米颗粒对角膜有刺激或阻塞鼻泪管的现象。MH纳米颗粒的共同滴注可能为提高眼科领域水溶性药物的生物利用度提供一种有用的方法。这些发现为设计旨在开发抗青光眼眼药的进一步研究提供了重要信息。
