High efficacy, rapid onset nanobiolosomes of sildenafil as a topical therapy for erectile dysfunction in aged rats.

Abstract

Developing topical sildenafil for local treatment of erectile dysfunction has been of great interest in pharmaceutical research. Sildenafil citrate (SC) exhibited a well-documented success for treatment of several types of erectile dysfunction. However, its oral use is limited by serious adverse effects, poor bioavailability, delayed onset, and drug-drug interactions. This work is the first to design and assess sildenafil-loaded bilosomes for topical local treatment of erectile dysfunction. Different sildenafil-loaded bilosomes were prepared and characterized. Permeability of selected formulations was conducted through full-thickness human skin. Optimized bilosomes integrating sodium tauroglycocholate (STGC) showed spherical shape with good particle size (133nm), high zeta potential (-53.6mV) and high entrapment efficiency (87.45%). Ex-vivo permeability study revealed that about 39% of the applied dose permeated within 15min. Furthermore, in-vivo appraisal of therapeutic efficacy was performed using aged male Sprague-Dawley rats. After single application of 2mg/kg sildenafil loaded in STGC-bilosomes, behavioral and biochemical evaluation was carried out. Behavioral assessment recorded an increased rats' potency manifested as 2 folds increase in intromission frequency and intromission ratio compared to untreated group. That was accompanied by significant increase in cGMP concentration in corpora cavernosa (P<0.0001) confirming increased potency. In conclusion, STGC-bilosomes could provide topical treatment of impotence with 20% of the oral dose and fast onset of action (10min).