006 Topical Abdominal Application of Curcumin-containing Nanoparticles Protects Erectile Function and Correlates with Corporal Expression of Inflammatory Markers (HO-1 and Nf- kB) in a Rat Model of Type-2-diabetes

Abstract

Although PDE5 inhibitors are the first line of therapy for men with erectile dysfunction (ED), patients with type 2 diabetes (T2D) are often refractory to this treatment. Chronic inflammation resulting from T2D contributes to the development of ED and curcumin, a natural anti-inflammatory compound, has recently been shown to have an effect on erectile function; however it is a molecule that exhibits poor oral bioavailability. To overcome this obstacle we designed a transdermal drug delivery system using nanoparticles to release curcumin (curc-NP) into the systemic blood circulation. The objective of this study is to investigate if curc-NP applied topically penetrate the skin and protect erectile function in a T2D rat model. Furthermore, we sought to study whether curcumin modulated the expression of erectile, inflammation and calcium sensitization markers in the corporal tissue. Zucker Diabetic Fat rats at 20 weeks of age were used as a model of T2D-related ED (3 groups; n=5). Treatment consisted of 6 applications over a 2 week period of curc-NP dispersed in coconut oil to the shaved rat abdomen (4 mg curcumin per application). Penetration of NP and curcumin release was confirmed by histology and in vivo multiphoton microscopy. Erectile function was determined by ICP/BP following cavernous nerve stimulation. Corporal tissue was removed after the surgery and total RNA was isolated using Trizol. Expression of markers of inflammation, erectile function, and smooth muscle calcium sensitization was assessed by Quantitative RT-PCR.