Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research I1 Apr 2014MP43-20 NANOTECHNOLOGY-BASED IMPLANT FOR LONG TERM TESTOSTERONE REPLACEMENT Eugenia Nicolov, Silvia Ferrati, Randy Goodall, Lee Hudson, Sharath Hosali, Michael Crowley, Ganesh Palapattu, Mohit Khera, and Alessandro Grattoni Eugenia NicolovEugenia Nicolov More articles by this author , Silvia FerratiSilvia Ferrati More articles by this author , Randy GoodallRandy Goodall More articles by this author , Lee HudsonLee Hudson More articles by this author , Sharath HosaliSharath Hosali More articles by this author , Michael CrowleyMichael Crowley More articles by this author , Ganesh PalapattuGanesh Palapattu More articles by this author , Mohit KheraMohit Khera More articles by this author , and Alessandro GrattoniAlessandro Grattoni More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1177AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Current delivery approaches in testosterone replacement therapy (TRT) generate fluctuations in testosterone plasma concentration. The objective of this study was to develop a constant, long-term TRT method. We have developed the implantable Personalized Molecular Drug-delivery System (PMDS) for the constant delivery of therapeutic agents using a silicon-based nanofluidics chip with nanochannels (density over 10,000,000/cm2) to control the rate of drug release via spatial and electrostatic nano-confinement with fabricated channel cross-section heights ranging from 2.5 to 250 nm. The sustained release is realized by constrained diffusion where the channel dimensions are precisely determined to create a steady diffusion of molecules. Here we demonstrate the use of the PMDS device to successfully delivery testosterone with long term constant plasma levels in rats. Methods In this study, the subcutaneous PMDS implant is made of machined titanium (see Figure) and contains the silicon-based nanofluidic chip, which is fabricated in a leading semiconductor foundry and acts as the rate controlling window. In vivo study: Three different testosterone formulations and a placebo formulation were aseptically loaded into the sterilized capsules and implanted into castrated male Sprague-Dawley rats (7-8 month old). A group of castrated rats received approximately 1/3 of a conventional testosterone pellet. A total of 54 rats were used including an intact control group. Blood samples were collected periodically for 126 days from the saphenous vein. Serum testosterone levels were measured by mass spectrometry. In vitro release of the formulations from identical capsules was measured in parallel by HPLC. Results The Figure shows the constant release of one testosterone formulation for 126 days. Intact and placebo serum testosterone levels are shown. Conclusions The PMDS implant delivers a relatively constant dose and mitigates the serum testosterone variability associated with implantable TRT modalities and will become an attractive alternative strategy for the long-term treatment of male hypogonadism. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e485-e486 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Eugenia Nicolov More articles by this author Silvia Ferrati More articles by this author Randy Goodall More articles by this author Lee Hudson More articles by this author Sharath Hosali More articles by this author Michael Crowley More articles by this author Ganesh Palapattu More articles by this author Mohit Khera More articles by this author Alessandro Grattoni More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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