摘要
血睾屏障(BTB)是男性体内最重要的供血障碍之一,它将精曲小管的上皮细胞,即睾丸的功能单位——精子产生的地方分成基地和顶部的隔间。功能上,BTB为减数分裂I / II和精子细胞发育提供了一个独特的微环境,其发生在心室中。远离宿主的免疫系统有助于睾丸的免疫状态。然而,BTB也是开发男性避孕药(例如,adjudin)的主要障碍,对生殖细胞产生影响,如通过破坏精子与Sertoli细胞的粘附,从而使生殖细胞从睾丸中脱落。除了在BTB中紧密黏附的Sertoli细胞可制约间质微血管腔部分,药物转运蛋白如P-糖蛋白和多药耐药相关蛋白1(MRP1),也存在处于睾丸之外的活性药物,从而限制了药物的生物利用度。在药物制剂的研究进展中,如药物颗粒的微细化(<50μm)和ß环糊精药物微粒化的共同粉碎已经通过大幅度的提高溶解度提高了避孕药的生物活性。在此,我们讨论药物制剂的进展,以adjudin为例。也强调了纳米技术将adjudin发送到多药磁性介质二氧化硅纳米颗粒的顶层去的用法。这些技术的进步,将大大提高我们的能力,为男性开发有效的非激素避孕药。
关键词: 睾丸;男性避孕;血睾屏障;adjudin;纳米技术。
Current Medicinal Chemistry
Title:Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) – Lesson from Adjudin
Volume: 23 Issue: 7
Author(s): Haiqi Chen, Dolores D. Mruk, Weiliang Xia, Michele Bonanomi, Bruno Silvestrini, Chuen-Yan Cheng
Affiliation:
关键词: 睾丸;男性避孕;血睾屏障;adjudin;纳米技术。
摘要: The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium of the seminiferous tubule, the functional unit of the testis, where spermatogenesis takes place, into the basal and the adluminal (apical) compartments. Functionally, the BTB provides a unique microenvironment for meiosis I/II and post-meiotic spermatid development which take place exclusively in the apical compartment, away from the host immune system, and it contributes to the immune privilege status of testis. However, the BTB also poses major obstacles in developing male contraceptives (e.g., adjudin) that exert their effects on germ cells in the apical compartment, such as by disrupting spermatid adhesion to the Sertoli cell, causing germ cell exfoliation from the testis. Besides the tight junction (TJ) between adjacent Sertoli cells at the BTB that restricts the entry of contraceptives from the microvessels in the interstitium to the adluminal compartment, drug transporters, such as P-glycoprotein and multidrug resistance-associated protein 1 (MRP1), are also present that actively pump drugs out of the testis, limiting drug bioavailability. Recent advances in drug formulations, such as drug particle micronization (<50 μm) and co-grinding of drug particles with ß-cyclodextrin have improved bioavailability of contraceptives via considerable increase in solubility. Herein, we discuss development in drug formulations using adjudin as an example. We also put emphasis on the possible use of nanotechnology to deliver adjudin to the apical compartment with multidrug magnetic mesoporous silica nanoparticles. These advances in technology will significantly enhance our ability to develop effective non-hormonal male contraceptives for men.
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Haiqi Chen, Dolores D. Mruk, Weiliang Xia, Michele Bonanomi, Bruno Silvestrini, Chuen-Yan Cheng , Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) – Lesson from Adjudin, Current Medicinal Chemistry 2016; 23 (7) . https://dx.doi.org/10.2174/0929867323666160112122724
DOI https://dx.doi.org/10.2174/0929867323666160112122724 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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