Formulação microemulsionada contendo mentol: uma terapia tópica inovadora para disfunção erétil

Abstract

Introduction: Currently, erectile dysfunction is associated with cardiovascular diseases, and some hypertensive patients do not respond well to conventional therapy. Activation of TRPM8 has shown relaxation of the internal pudendal artery in rats, suggesting a potential treatment for hypertension-related erectile dysfunction. Menthol, a TRPM8 agonist, poses challenges in use due to its solubility and volatility. This study aimed to develop and evaluate the efficacy of a menthol-containing microemulsion for topical treatment of erectile dysfunction in an animal model with essential hypertension, focusing on erectile tissues. Methods: Firstly, a pseudo-ternary diagram was created to select a specific mixture of oil, surfactant, co-surfactant, and water. This mixture was enriched with menthol and thoroughly studied. The resulting microemulsion was modified with the addition of xanthan gum, and its influence was investigated alongside menthol. Transmission electron microscopy (TEM), dynamic light scattering, and small-angle X-ray scattering (SAXS) analyses revealed droplets with a smaller average diameter. Stability assays were conducted to assess the shelf life of the microemulsion system for 90 days. Studies on 10-week-old SHR and Wistar rats involved daily topical application of menthol-containing microemulsion for 21 days on the penile region, with results analyzed in tissues from the corpus cavernosum (CC), internal pudendal artery (IPA), and superior mesenteric artery (SMA). Results: The pseudo-ternary diagram was used to select a mixture of oil, surfactant, co-surfactant, and water. This mixture was enriched with menthol and thoroughly studied. The resulting microemulsion was modified with the addition of XG. Transmission electron microscopy (TEM) analyses showed droplets with an average diameter smaller than 120 nm, confirmed by dynamic light scattering and small-angle X-ray scattering (SAXS). The mixture conformation was droplet-like, as observed by SAXS and TEM. Topical treatment with menthol in SHR rats with ED significantly reduced blood pressure but did not affect body development. It decreased responsiveness to vasoconstrictors in the corpus cavernosum and increased response to vasodilators. It also altered responsiveness of the internal pudendal artery but did not affect deeper arteries like the superior mesenteric artery. Conclusion: Our data suggest that the microemulsion holds potential in treating erectile dysfunction associated with hypertension. Topical menthol treatment reduced blood pressure and improved artery responsiveness, as well as enhancing sildenafil effectiveness. We are developing an innovative menthol-based therapy with promising prospects for future interventions.