Modulating the Blood–Testis Barrier Towards Increasing Drug Delivery

Testicular cells produce several biologically active peptides that exert their downstream effects by activating distinct signaling proteins. These biomolecules are now known to support spermatogenesis and effectively enhance paracellular and transcellular diffusion of drugs (e.g., adjudin) across the blood–testis barrier (BTB). We briefly discuss the biomolecules that maintain the BTB: these provide new insights into how the BTB can be modulated to allow therapeutic drugs, including male contraceptives, to be transported across the BTB and more generally across blood–tissue barriers. Information gleaned by studying the BTB, as well as other blood–tissue barriers, augments our understanding of blood–tissue barriers and provides new insights into how drugs can be delivered to organs that are effectively protected by tissue barriers. Blood–tissue barriers such as the blood–brain barrier (BBB) and the BTB, as well as drug transporters at these sites, pose a major barrier to drug delivery.Biologically active peptides produced locally in the testis are known to modify BTB function by enhancing paracellular and/or transcellular drug diffusion.These bioactive peptides and players in their downstream signaling cascades may be used to enhance drug transport across BTB, and knowledge gathered from these studies may be extrapolated to other blood–tissue barriers.