Department of Zoology, Faculty of Science, Sohag University, Sohag, 82524, Egypt.
Department of Organ Anatomy and Nanomedicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
Histochem Cell Biol. 2021 Jun;155(6):683-698. doi: 10.1007/s00418-021-01974-1. Epub 2021 Mar 3.
Recently the vaginal route consider as an ideal route for drug delivery systems (DDS) administration. This is because, it is suitable for lower drug dosage, higher drug concentration in the genital tract tissues and lower drug concentration in pregnant women blood circulation. However, the vaginal route administration faces many challenges due to the physiology as well as the complexity of vaginal tissue histology. Here in this study, during diestrus stage (optimal condition for foreign substance internalization), single or dual size of fluorescent thiol-organosilica nanoparticles (tOS-NPs) were administrated intravaginally. The biodistribution and reactivity of tOS-NPs in different tissues of the female genital tract were investigated under the fluorescence microscope. Furthermore, using immunohistochemical staining, the expression of F4/80 protein and the role of macrophages in transport and re-location of tOS-NPs from vaginal lumen into different genital tissues or other organs were investigated. This study showed that, tOS-NPs size and type of tissue are important in biodistribution and uptake of tOS-NPs in the genital tract. Small size (100 nm) of tOS-NPs was highly accumulated in the genital tract tissues especially endometrial epithelium compared with large tOS-NPs (1000 nm). Contradictory, the large size induced the expression of F4/80 protein and the number of vaginal macrophages compared with small size. However, both small and large sizes of tOS-NPs were found co-localized with F4/80 macrophages, located in the vaginal, endometrial and ovarian tissues. The tOS-NPs intravaginally administrated were found in the splenic tissues, indicating its ability to enter the blood circulation from the vaginal lumen. Additionally, the high accumulation of tOS-NPs in the endometrial epithelium indicated the endometrial first pass effect of tOS-NPs. As a result, high concentration of tOS-NPs in the endometrial epithelium may reduce the concentration of tOS-NPs-based DDS in the blood circulation and their side effects. Furthermore, during vaginal tissue optimal condition (diestrus stage), understanding the fate and biodistribution of tOS-NPs will introduce important data about the development of save and effective DDS for the pregnant women.
最近，阴道途径被认为是药物传递系统（DDS）给药的理想途径。这是因为，它适合于较低的药物剂量、在生殖道组织中更高的药物浓度和在孕妇血液循环中更低的药物浓度。然而，由于阴道的生理学以及阴道组织组织学的复杂性，阴道途径给药面临着许多挑战。在这项研究中，在发情期（异物内化的最佳条件）期间，阴道内给予单一或双重大小的荧光硫醇-有机硅纳米颗粒（tOS-NPs）。荧光显微镜下研究了 tOS-NPs 在女性生殖道不同组织中的分布和反应性。此外，通过免疫组织化学染色，研究了 F4/80 蛋白的表达以及巨噬细胞在 tOS-NPs 从阴道腔转移到不同生殖道组织或其他器官中的作用。本研究表明，tOS-NPs 的大小和组织类型对 tOS-NPs 在生殖道中的分布和摄取很重要。与大 tOS-NPs（1000nm）相比，小 tOS-NPs（100nm）高度积累在生殖道组织中，特别是子宫内膜上皮中。相反，大尺寸诱导了 F4/80 蛋白的表达和阴道巨噬细胞的数量，与小尺寸相比。然而，小尺寸和大尺寸的 tOS-NPs 都与位于阴道、子宫内膜和卵巢组织中的 F4/80 巨噬细胞共定位。阴道内给予的 tOS-NPs 被发现存在于脾组织中，表明其能够从阴道腔进入血液循环。此外，tOS-NPs 在子宫内膜上皮中的高积累表明 tOS-NPs 对子宫内膜的首过效应。因此，tOS-NPs 在子宫内膜上皮中的高浓度可能会降低基于 tOS-NPs 的 DDS 在血液循环中的浓度及其副作用。此外，在阴道组织最佳条件（发情期）期间，了解 tOS-NPs 的命运和分布将为开发针对孕妇的安全有效的 DDS 提供重要数据。
