Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction.
BACKGROUND
Nanoparticles represent a potential novel mechanism for transdermal delivery of erectogenic agents directly to the penis.


OBJECTIVE
To determine if nanoparticles encapsulating known erectogenic agents (tadalafil, sialorphin, and nitric oxide [NO]) can improve erectile function in a rat model of erectile dysfunction (ED) as a result of aging (the Sprague-Dawley retired breeder rat).


METHODS
Nanoparticles encapsulating the erectogenic agents were applied as a gel to the glans and penile shaft of anesthetized Sprague-Dawley rats and the intracorporal pressure/blood pressure (ICP/BP) monitored for up to 2 hours with or without stimulation of the cavernous nerve. Control nanoparticles were made without encapsulating erectogenic agents and applied in a similar manner in separate experiments.


RESULTS
Nanoparticles encapsulating NO caused spontaneous visible erections in the rat, with an average time of onset of 4.5 minutes, duration of 1.42 minutes, and ICP/BP of 0.67 +/- 0.14. The sialorphin nanoparticles also caused visible spontaneous erections after an average of 4.5 minutes, with a duration of 8 minutes and ICP/BP ratio of 0.72 +/- 0.13. The difference in the erectile response between groups of animals treated with NO or sialorphin nanoparticles was significantly different from the control group treated with empty nanoparticles (P < 0.05) Tadalafil nanoparticles showed a significant increase in the mean ICP/BP (0.737 +/- 0.029) following stimulation of the cavernous nerve (4 mA) 1 hour after application of the nanoparticles with a visibly improved erectile response.


CONCLUSIONS
Nanoparticles encapsulating three different erectogenic agents resulted in increased erectile function when applied to the penis of a rat model of ED. Nanoparticles represent a potential novel route for topical delivery of erectogenic agents which could improve the safety profile for existing orally administered drugs by avoiding effects of absorption and first-pass metabolism, and would be less hazardous than injection.
Han
George
G
Department of Biophysics and Physiology, Albert Einstein College of Medicine, Bronx, NY, USA.
Tar
Moses
M
Kuppam
Dwaraka S R
DS
Friedman
Adam
A
Melman
Arnold
A
Friedman
Joel
J
Davies
Kelvin P
KP
D000279:Administration, Cutaneous; D000367:Age Factors; D000818:Animals; D002243:Carbolines / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D018783:Impotence, Vasculogenic / Q000188:drug therapy*; D008297:Male; D053769:Nanocapsules / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000008:administration & dosage*; D010410:Penile Erection / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011480:Protease Inhibitors / Q000008:administration & dosage*; D011498:Protein Precursors / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000008:administration & dosage*; D000068581:Tadalafil
D002243:Carbolines; D016166:Free Radical Scavengers; D053769:Nanocapsules; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D011480:Protease Inhibitors; D011498:Protein Precursors; D012471:Salivary Proteins and Peptides; C066861:Smr3b protein, rat; D009569:Nitric Oxide; D000068581:Tadalafil