title: 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.
authors.affiliation: The Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX, 77030, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferrati
authors.forename: Eugenia
authors.initials: E
authors.lastname: Nicolov
authors.forename: Shyam
authors.initials: S
authors.lastname: Bansal
authors.forename: Erika
authors.initials: E
authors.lastname: Zabre
authors.forename: Thomas
authors.initials: T
authors.lastname: Geninatti
authors.forename: Arturas
authors.initials: A
authors.lastname: Ziemys
authors.forename: Lee
authors.initials: L
authors.lastname: Hudson
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.forename: Randal
authors.initials: R
authors.lastname: Goodall
authors.forename: Mohit
authors.initials: M
authors.lastname: Khera
authors.forename: Ganesh
authors.initials: G
authors.lastname: Palapattu
authors.forename: Alessandro
authors.initials: A
authors.lastname: Grattoni
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D016503:Drug Delivery Systems; D004343:Drug Implants / Q000008:administration & dosage* / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000097:blood; D007700:Kinetics; D008163:Luminescent Measurements; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D009919:Orchiectomy; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D004343:Drug Implants; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: androgen deficiency; cyclodextrin; nanochannel implants; sustained release; testosterone