Topical application of Sildenafil-nanoparticles (proximal and distal) improve erectile function in an aging-rat model of erectile dysfunction
Tar, MT1; Draganski, A1; Friedman, J1; Davies, KP1
1: Albert Einstein College of Medicine, United States
Objective(s); Recently our group demonstrated the feasibility of using topical application of a nanoparticle (np) delivery system encapsulating nitric oxide (NO-np) and tadalafil (tadalafil-np) to improve erectile function in animal models of erectile dysfunction (ED). We report here studies suggesting that topically applied sildenafil-np improves erectile function in an aging-rat model of ED. These studies have the long-term goal of developing a topically applied treatment for men with ED who are refractory to, or who cannot tolerate, the side-effects of current treatment options.
Material and Method(s); Ten-retired Male Sprague-Dawley rats (approximately 15-months old) were used as a model of age-related ED. Treatment consisted of application of a sildenafil-np suspension (equivalent to about 1mg sildenafil) to the rat corporal dermis (local treatment) on 5-rats. We determined the ICP/BP response following cavernous nerve (CN) stimulation at 0.75 and 4 mA prior to, and at 15-25 and 35-45 minutes after administration of the sildenafil-np. To determine if the effect was local or might have a systemic component, we performed the same experiments on an additional 5-rats, but applied the sildenafil-np only to the shaved abdominal region.
Result(s); Prior to sildenafil-np treatment, 0.75 and 4 mA stimulation of the CN resulted in an average ICP/BP of 0.516 (SEM=0.04) and 0.502 (SEM=0.06), respectively. 15-25 minutes after topical application to the corporal dermis of the sildenafil-np, 4mA stimulation of the CN improved the erectile response in 4 of the 5 animals studies (P <0.05) by 22% to an average ICP/BP of 0.6 (SEM 0.07). 35-45 min post-treatment at 4mA CN stimulation there was a similar trend for improved erectile response (though not reaching significance). Animals with distal (abdominal) application of the sildenafil-np in the same manner as per the corpora application showed no improvement in erectile function.
Conclusion(s): These results suggest that an alternative route to orally administered sildenafil to treat ED is topically through the use of our nanoparticle delivery system. Although orally administered sildenafil is generally well-tolerated, topical application of sildenafil-np may represent a significant improvement because of potentially lowered doses for efficacy, improved safety profile, speed of efficacy and the potential to treat patients that are refractory to existing treatments. This new data shows a statistically improved erectile function when sildenafil-np is topically applied on the corpora (local) but no improvement when applied to the abdomen(distal) suggesting the lack of systemic effect on local application.
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