Delivering Enhanced Testosterone Replacement Therapy through Nanochannels

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.

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Unexpected behaviors in molecular transport through size-controlled nanochannels down to the ultra-nanoscale

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Impedance characterization, degradation, and in vitro biocompatibility for platinum electrodes on BioMEMS

“…This control is relevant to a broad spectrum of biomedical applications, including drug delivery (Desai et al 1999; Ferrati et al 2013, In press; Celia et al 2014), molecular sieving (Fu et al 2007), cell sorting (Gossett et al 2010), and cell transplantation (Desai et al 1998; Sabek et al 2013). In drug delivery, the ability to fine tune release profiles for specific therapeutic agents is highly beneficial in personalized treatments requiring dose titration or synchronization with the biological clock, the fundamental principle in chronotherapy (Smolensky and Peppas 2007; Youan 2010).…”

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