Delivering Enhanced Testosterone Replacement Therapy through Nanochannels

Silvia Ferrati, Eugenia Nicolov, Shyam Bansal, Erika Zabre, Thomas Geninatti, Arturas Ziemys, Lee Hudson, Mauro Ferrari, Randal Goodall, Mohit Khera, Ganesh Palapattu, Alessandro Grattoni

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In this study, an implantable nanochannel system is investigated as an alternative delivery strategy for the long-term sustained and constant release of testosterone. In vitro release tests are performed using a dissolution set up, with testosterone and testosterone:2-hydroxypropyl-β-cyclodextrin (TES:HPCD) 1:1 and 1:2 molar ratio complexes release from the implantable nanochannel system and quantify by HPLC. 1:2 TES:HPCD complex stably achieve 10-15 times higher testosterone solubility with 25-30 times higher in vitro release. Bioactivity of delivered testosterone is verified by LNCaP/LUC cell luminescence. In vivo evaluation of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels by liquid chromatography mass spectrometry (LC/MS) and multiplex assay is performed in castrated Sprague-Dawley rats over 30 d. Animals are treated with the nanochannel implants or degradable testosterone pellets. The 1:2 TES:HPCD nanochannel implant exhibits sustained and clinically relevant in vivo release kinetics and attains physiologically stable plasma levels of testosterone, LH, and FSH. In conclusion, it is demonstrated that by providing long-term steady release 1:2 TES:HPCD nanochannel implants may represent a major breakthrough for the treatment of male hypogonadism.

Original languageEnglish (US)
Pages (from-to)446-451
Number of pages6
JournalAdvanced Healthcare Materials
Volume4
Issue number3
DOIs
StatePublished - Feb 1 2015

Keywords

  • Androgen deficiency
  • Cyclodextrin
  • Nanochannel implants
  • Sustained release
  • Testosterone

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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