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Size-dependent biodistribution of thiol-organosilica nanoparticles and F4/80 protein expression in the genital tract of female mice after intravaginal administration
Histochemistry and Cell Biology ( IF 2.1 ) Pub Date : 2021-03-03 , DOI: 10.1007/s00418-021-01974-1
Aziz Awaad 1 , Michihiro Nakamura 2
Affiliation  

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.



中文翻译:

阴道内给药后雌性小鼠生殖道中硫醇-有机二氧化硅纳米颗粒的大小依赖性生物分布和 F4/80 蛋白表达

最近阴道途径被认为是给药系统 (DDS) 给药的理想途径。这是因为,它适用于较低的药物剂量、较高的生殖道组织药物浓度和较低的孕妇血液循环中的药物浓度。然而,由于生理学以及阴道组织组织学的复杂性,阴道给药面临许多挑战。在这项研究中,在发情期(异物内化的最佳条件),阴道内施用单或双尺寸的荧光硫醇 - 有机硅纳米颗粒(tOS-NPs)。在荧光显微镜下研究了 tOS-NPs 在女性生殖道不同组织中的生物分布和反应性。此外,使用免疫组织化学染色,研究了 F4/80 蛋白的表达和巨噬细胞在 tOS-NPs 从阴道腔转运和重新定位到不同生殖器组织或其他器官中的作用。该研究表明,tOS-NPs 的大小和组织类型对于 tOS-NPs 在生殖道中的生物分布和吸收很重要。与大的 tOS-NPs (1000 nm) 相比,小尺寸 (100 nm) 的 tOS-NPs 在生殖道组织中高度积累,尤其是子宫内膜上皮。相反,与小尺寸相比,大尺寸诱导了F4/80蛋白的表达和阴道巨噬细胞的数量。然而,发现小尺寸和大尺寸的 tOS-NPs 都与 F4/80 共定位 该研究表明,tOS-NPs 的大小和组织类型对于 tOS-NPs 在生殖道中的生物分布和吸收很重要。与大的 tOS-NPs (1000 nm) 相比,小尺寸 (100 nm) 的 tOS-NPs 在生殖道组织中高度积累,尤其是子宫内膜上皮。相反,与小尺寸相比,大尺寸诱导了F4/80蛋白的表达和阴道巨噬细胞的数量。然而,发现小尺寸和大尺寸的 tOS-NPs 都与 F4/80 共定位 该研究表明,tOS-NPs 的大小和组织类型对于 tOS-NPs 在生殖道中的生物分布和吸收很重要。与大的 tOS-NPs (1000 nm) 相比,小尺寸 (100 nm) 的 tOS-NPs 在生殖道组织中高度积累,尤其是子宫内膜上皮。相反,与小尺寸相比,大尺寸诱导了F4/80蛋白的表达和阴道巨噬细胞的数量。然而,发现小尺寸和大尺寸的 tOS-NPs 都与 F4/80 共定位 与小尺寸相比,大尺寸诱导F4/80蛋白的表达和阴道巨噬细胞的数量。然而,发现小尺寸和大尺寸的 tOS-NPs 都与 F4/80 共定位 与小尺寸相比,大尺寸诱导F4/80蛋白的表达和阴道巨噬细胞的数量。然而,发现小尺寸和大尺寸的 tOS-NPs 都与 F4/80 共定位+巨噬细胞,位于阴道、子宫内膜和卵巢组织中。在脾组织中发现了阴道内给药的 tOS-NPs,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 的子宫内膜首过效应。因此,子宫内膜上皮中高浓度的 tOS-NPs 可能会降低血液循环中基于 tOS-NPs 的 DDS 的浓度及其副作用。此外,在阴道组织最佳状态(发情期)期间,了解 tOS-NPs 的命运和生物分布将为孕妇提供有关开发保存和有效 DDS 的重要数据。

更新日期:2021-03-03
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