The nanochannel delivery system for constant testosterone replacement therapy.
BACKGROUND
The goal of testosterone replacement is to provide long-term physiological supplementation at sufficient levels to mitigate the symptoms of hypogonadism.


OBJECTIVE
The objective of this work is to determine if the implantable nanochannel delivery system (nDS) can present an alternative delivery strategy for the long-term sustained and constant release of testosterone.


METHODS
A formulation of common testosterone esters (F1) was developed to enable nanochannel delivery of the low water soluble hormone. In vivo evaluation of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels by liquid chromatography/mass spectrometry and a multiplex assay, respectively, in castrated Sprague-Dawley rats implanted with nDS-F1 implants or polymeric pellets was performed over a 6-month period. The percent of testosterone concentrations observed that fell within the normal range of testosterone levels for each animal was calculated and used to compare the study groups.


METHODS
Sustain release of testosterone in vivo for over 6 months.


RESULTS
The subcutaneous release of F1 from nDS implants exhibited sustained in vivo release kinetics and attained stable clinically relevant plasma testosterone levels. Plasma LH and FSH levels were significantly diminished in nDS-F1 implant-treated animals, confirming biological activity of the released testosterone.


CONCLUSIONS
In conclusion, we demonstrate that nDS-F1 implants represents a novel approach for the treatment of male hypogonadism. Further studies will be performed in view of translating the technology to clinical use.
The Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
Silvia
S
Ferrati
The Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
Eugenia
E
Nicolov
The Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
Erika
E
Zabre
The Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
Thomas
T
Geninatti
Department of Surgery, Houston Methodist Hospital, Houston, TX, USA.
Beverly A
BA
Shirkey
NanoMedical Systems Inc., Austin, TX, USA.
Lee
L
Hudson
NanoMedical Systems Inc., Austin, TX, USA.
Sharath
S
Hosali
NanoMedical Systems Inc., Austin, TX, USA.
Michael
M
Crawley
Department of Urology, Baylor College of Medicine, Houston, TX, USA.
Mohit
M
Khera
Department of Urology, University of Michigan, Ann Arbor, MI, USA.
Ganesh
G
Palapattu
The Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
Alessandro
A
Grattoni
D000818:Animals; D004343:Drug Implants / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007006:Hypogonadism / Q000188:drug therapy* / Q000473:pathology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D004343:Drug Implants; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
Androgen Deficiency; Nanochannel Implants; Sustained Release; Testosterone