Drug delivery to the testis: current status and potential pathways for the development of novel therapeutics

Abstract

Nanotechnology has been increasingly utilized for the targeting and delivery of novel therapeutic agents to different tissues and cell types. The current therapeutic options for testicular disorders fall short in many instances due to difficulty traversing the blood-testis barrier, systemic toxicities, and complicated dosing regiments. For testicular tissue, potential targeting can be obtained either via anatomic methods or specific ligands such as luteinizing hormone or follicle-stimulating hormone analogs. Potential novel therapeutic agents include DNA, RNA, cytokines, peptide receptor antagonists, peptide receptor agonists, hormones, and enzymes. Nanotherapeutic treatment of testicular cancer, infertility, testicular torsion, orchalgia, hypogonadism, testicular infections, and cryptorchidism within the framework of potential target cells are an emerging area of research. While there are many potential applications of nanotechnology in drug delivery to the testis, this remains a relatively unexplored field. This review highlights the current status as well as potential future of nanotechnology in the development of novel therapeutics for testicular disorders.

Highly Active Antiretroviral Therapy (HAART) and Testicular Morphology: Current Status and a Case for a Stereologic Approach

“…The testis plays a significant role in the process of reproduction by its uniqueness in structure, location, and function. Enclosed in a three-layered capsule (of tunica; Brooks, 2007), it is compactly stuffed with seminiferous tubules that make up 60% to 95% of the 30-mL testicular volume that represents the site for spermatogenesis ( Figure 1; Sharpe, 1986;Snow-Lisy et al, 2011). Recently, the association between HAART and sexual dysfunction in HIV-infected patients has become a subject of intense research by experts.…”

“…Spermatogenesis is the ordered maturation of spermatogonia into functional spermatozoa, and it takes about 72 days to complete (Sharpe, 1986). This complex process requires extensive restructuring in the Sertoli cells, which are the chaperones of spermatogenesis and form the BTB, and thus are rational targets for drugs/toxicants (Figure 1; Snow‐Lisy et al, 2011). Sperm morphology is regarded as a significant prognostic factor for fertilization and pregnancy; hence, abnormal sperm morphology is one of the most common factors in male infertility (Franken, 1998).…”

Anatomical Targeting Improves Delivery of Unconjugated Nanoparticles to the Testicle

“…1, 2 Targeted drug delivery to the testes could be used for the treatment of numerous conditions; including but not limited to, the treatment of testicular torsion and infertility associated with elevated reactive oxygen species. [2][3][4][5][6] At this point, NPs ability to penetrate the testicle has not been evaluated.…”

“…Data are expressed as the mean ± the standard error of the mean. Data were excluded if the animal died prior to end point(2) or the sample was lost or contaminated (1/1). P values under 0.05 were considered statistically significant (JMP 9 software, Cary, NC).Results:Formulation and characterization of NPs: The mean diameter of NPs dispersed in water (mean hydrodynamic diameter) ranged from 279.4-315.6 nm(Figure 1).…”

The Male Genital Tract in the Era of Highly Active Antiretroviral Therapy (HAART): Implication for Antioxidant Therapy

“…However, the entire process of spermatogenesis itself involves series of morphological and biochemical transformation that will eventually result in the formation of a mature sperm cell capable of fertilizing the female counterpart-the ovum. Due to this complexity, various pathologies (infertility, oxidative stress from torsion, cancer, hypogonadism or disorders of spermatogenesis caused by toxicant exposure, varicocele or aging) have been associated with this process targeting various cell types [2]. While the sperm cell plasma membrane is high in polyunsaturated fatty acids (PUFA) making it especially vulnerable to free radical attack [3], it is only recently that cellular redox activity is found to be important for sperm to attain a functionally competent state to fertilize an oocyte [4].…”