Nagai Noriaki, Iwai Yoshie, Deguchi Saori, Otake Hiroko, Kanai Kazutaka, Okamoto Norio, Shimomura Yoshikazu
Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Department of Small Animal Internal Medicine, School of Veterinary Medicine, University of Kitasato, Towada, Aomori 034-8628, Japan.
Nanomaterials (Basel). 2019 May 19;9(5):768. doi: 10.3390/nano9050768.
We previously found the instillation of sericin to be useful as therapy for keratopathy with or without diabetes mellitus. In this study, we investigated whether a combination of solid magnesium hydroxide nanoparticles (MHN) enhances epithelial corneal wound healing by sericin using rabbits, normal rats and type 2 diabetes mellitus rats with debrided corneal epithelium (ex vivo and in vivo studies). Ophthalmic formulations containing sericin and MHN (N-Ser) were prepared using a bead mill method. The mean particle size of the N-Ser was 110.3 nm at the time of preparation, and 148.1 nm one month later. The instillation of N-Ser had no effect on the amount of lacrimal fluid in normal rabbits (in vivo), but the MHN in N-Ser was found to expand the intercellular space in ex vivo rat corneas. In addition, the instillation of N-Ser increased the phosphorylation of Extracellular Signal-regulated Kinase (ERK)1/2, a factor involved in cell adhesion and cell proliferation in the corneal epithelium, in comparison with the instillation of sericin alone. The combination with MHN enhanced epithelial corneal wound healing by sericin in rat debrided corneal epithelium (in vivo). This study provides significant information to prepare potent drugs to cure severe keratopathy, such as diabetic keratopathy.
我们之前发现,丝胶蛋白滴眼剂对伴有或不伴有糖尿病的角膜病均有治疗作用。在本研究中,我们使用家兔、正常大鼠以及角膜上皮清创的2型糖尿病大鼠,研究了固体氢氧化镁纳米颗粒(MHN)与丝胶蛋白联合使用是否能促进角膜上皮伤口愈合(体外和体内研究)。采用珠磨法制备了含丝胶蛋白和MHN的眼科制剂(N-Ser)。制备时N-Ser的平均粒径为110.3nm,1个月后为148.1nm。N-Ser滴眼对正常家兔泪液量无影响(体内研究),但发现N-Ser中的MHN可扩大体外培养的大鼠角膜细胞间隙。此外,与单独滴注丝胶蛋白相比,滴注N-Ser可增加细胞外信号调节激酶(ERK)1/2的磷酸化,ERK1/2是参与角膜上皮细胞黏附和增殖的一个因子。在大鼠角膜上皮清创模型中(体内研究),MHN与丝胶蛋白联合使用可增强丝胶蛋白促进角膜上皮伤口愈合的作用。本研究为制备治疗严重角膜病(如糖尿病性角膜病)的有效药物提供了重要信息。