Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) – Lesson from Adjudin
2016
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 s-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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