Delivering enhanced testosterone replacement therapy through nanochannels

Adv Healthc Mater. 2015 Feb 18;4(3):446-51. doi: 10.1002/adhm.201400348. Epub 2014 Oct 1.


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.

Keywords: androgen deficiency; cyclodextrin; nanochannel implants; sustained release; testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Animals
  • Drug Delivery Systems
  • Drug Implants / administration & dosage*
  • Drug Implants / pharmacology
  • Follicle Stimulating Hormone / blood
  • Kinetics
  • Luminescent Measurements
  • Luteinizing Hormone / blood
  • Male
  • Nanostructures / administration & dosage*
  • Nanostructures / chemistry
  • Orchiectomy
  • Rats, Sprague-Dawley
  • Testosterone / administration & dosage*
  • Testosterone / blood
  • beta-Cyclodextrins / chemistry


  • Drug Implants
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Testosterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone