Clinical trials of intratesticular administration of nanostructured lipid carriers encapsulated alpha-mangostin: Safety and efficacy on feline reproductive health.

Autor: Leelakajornkit S; Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, 39 Henri-Dunant Rd., Pathumwan, Bangkok, 10330 Thailand., Boonthum C; Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, 39 Henri-Dunant Rd., Pathumwan, Bangkok, 10330 Thailand., Borikkappakul P; Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, 39 Henri-Dunant Rd., Pathumwan, Bangkok, 10330 Thailand., Yata T; Unit of Biochemistry, Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330 Thailand., Yostawonkul J; National Nanotechnology Centre, National Science and Technology Development Agency, Phahonyothin Rd., Klong Luang, Pathumthani 12120 Thailand., Ponglowhapan S; Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, 39 Henri-Dunant Rd., Pathumwan, Bangkok, 10330 Thailand. Electronic address: sponglowhapan@gmail.com.
Jazyk: angličtina
Zdroj: Theriogenology [Theriogenology] 2025 Jan 01; Vol. 231, pp. 240-249. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1016/j.theriogenology.2024.10.022
Abstrakt: Surgical castration is a primary method for controlling male fertility, but it is impractical for large-scale population control of stray animals. Developing nanoparticle-mediated sterilants that induce cell apoptosis rather than necrosis is a complex and promising area of research. This study aimed to investigate the impact of intratesticular administration of alpha-mangostin encapsulated in nanostructured lipid carriers (AM-NLC) on testicular changes and any associated adverse effects over a 168-day observation period. Thirty-two healthy mature tomcats were enrolled. None of the cats treated with either AM-NLC (n = 28) or blank NLC (n = 4) exhibited noticeable complications related to pain or stress throughout the study, as assessed by clinical examination, blood profiles, and serum amyloid A levels. Histopathological analysis of AM-NLC treated cats revealed seminiferous epithelium degeneration, leading to defective tubules. Key findings included germ cell depletion, disorganized spermatogenic cells without spermatids in certain areas, apoptotic bodies, and intracytoplasmic vacuolization. The intertubular compartment showed no signs of inflammation, hyalinization, fibrosis, or necrosis. Despite widespread degeneration, some normal tubules were present in focal areas. The severity score of seminiferous tubule degeneration significantly increased from day 56 onwards (P < 0.05), suggesting a gradual and progressive compromise of the seminiferous epithelium. In contrast, testes from the blank-NLC group exhibited normal spermatogenesis. Overall, there were no significant changes in the volume of dissected testes, serum testosterone levels, or apoptotic index in AM-NLC-treated cats (P > 0.05). In conclusion, this study represents the first in vivo investigation of apoptotic-inducing agents as a novel nanomedicine-based antifertility compound for non-surgical castration in male animals. While the AM-NLC formulation proved safe for intratesticular administration, it failed to induce infertility in cats, as epididymal spermatozoa persisted throughout the study. Further research into alternative apoptosis-inducing nanomedicine sterilants remains both essential and challenging.
Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this manuscript. No financial or personal relationships have influenced the work reported in this study.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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