Abstract
Background and Objective: Erectile dysfunction (ED) is a common disease in diabetic patients. Alprostadil (Prostaglandin E1, PGE1) has shown higher success rates compared with phosphodiesterase type 5 inhibitors (PDE-5) in the treatment of ED. The combined formula of PGE1 with D-tocopheryl polyethylene glycol succinate (TPGS) was aimed to find a novel treatment for diabetic patients suffering from ED via protecting epithelial cells that lined penile vessels from the oxidative stress. Materials and Methods: PGE1-TPGS was prepared either with labrasol, polyethylene glycol 200 (PEG 200) or a mixture of labrasol and PEG 200, F1, F2 and F3 respectively. The prepared formulations were characterized for morphology and zeta potential and then were added to 1.5% of hydroxypropyl methyl cellulose solution to form topical hydrogel. Drug release study for all investigated formulations was conducted in comparison with raw-PGE1 and tested in endothelial cells (EA. hy926) under stress condition. Results:The obtained data revealed that PGE1-TPGS prepared with labrasol achieved the highest particle size while, PGE1-TPGS formula of PEG 200 and labrasol mixture showed the smallest particle size. Transmission electron microscope (TEM) images of the prepared formulations showed spherical shape micelles. Oxidative stress investigation showed a dramatic improvement in epithelial cell survival that attenuated the permeation enhancer's cytotoxicity. F1, F2 and F3 treatments showed improved cell viability when compared with blank formulations. At concentration 10 mu g mL(-1), results showed that the investigated formulations improved cell viability from 9.13% (F1 blank), 7.55% (F2 blank) and 8.82% (F3 blank) to 90.52, 91.27 and 93.94% for F1, F2 and F3 formulations, respectively. Conclusion: The study revealed that combination of PGE1 with TPGS micelles formula loaded topical gel could be a successful strategy for the treatment of ED in diabetic patients.