Effective delivery of male contraceptives behind the blood-testis barrier (BTB)—Lesson from adjudin
The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium 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 testis its immune privilege status. However, the BTB also poses major obstacles in developing male contraceptives (e.g., adjudin) that exert their effects to germ cells in the apical compartment, such as by disrupting spermatid adhesion to the Sertoli cell, causing germ cell exfoliation from the testis. Besides of 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 significant increase in solubility. Herein, we will discuss development in drug formulations using adjudin as an example. We’ll also put some 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.
Chen, Haiqi, Dolores D. Mruk, Weiliang Xia, Michele Bonanomi, Bruno Silvestrini, and C. Yan Cheng. 2016. "Effective delivery of male contraceptives behind the blood-testis barrier (BTB)—Lesson from adjudin," Current Medicinal Chemistry 23(7): 701–713.