Antifungal efficacy of atorvastatin-containing emulgel in the treatment of oral and vulvovaginal candidiasis

Abstract

Drug repositioning has been an important ally in the search for new antifungal drugs. Statins are drugs that act to prevent sterol synthesis in both humans and fungi and for this reason they are promissory candidates to be repositioned to treat mycoses. In this study we evaluated the antifungal activity of atorvastatin by in vitro tests to determine the minimum inhibitory concentration against azole resistant Candida albicans and its mechanisms of action. Moreover, the efficacy of both atorvastatin-loaded oral and vaginal emulgels (0.75%, 1.5% and 3% w/w) was evaluated by means of in vivo experimental models of oral and vulvovaginal candidiasis, respectively. The results showed that atorvastatin minimal inhibitory concentration against C. albicans was 31.25 μg/ml. In oral candidiasis experiments, the group treated with oral emulgel containing 3.0% atorvastatin showcased total reduction in fungal load after nine days of treatment. Intravaginal delivery atorvastatin emulgel showed considerable effectiveness at the concentration of 3% (65% of fungal burden reduction) after nine days of treatment. From these findings, it is possible to assert that atorvastatin may be promising for drug repositioning towards the treatment of these opportunistic mycoses. Lay Summary Atorvastatin is a statin drug that presents antifungal activity. This study showed that atorvastatin-containing oral and vaginal emulgels were able to treat vulvovaginal and oral candidiasis of infected animal model. Therefore, we showcased that atorvastatin may be a possible therapeutic agent in order to be a used to control opportunistic mucosal fungal infections caused by Candida albicans.

Clinical Manifestations of Human Exposure to Fungi

“…In cases of recurrent vulvovaginitis or the presence of antifungal resistance strains, several alternative or complementary approaches have been developed, including the use of acid boric, flucytosine [ 180 ], ibrexafungerp [ 181 ], spilanthol [ 182 ], atorvastatin [ 183 ], probiotics [ 184 ], and p-Coumaric acid [ 178 ].…”

Drug Repurposing in Medical Mycology: Identification of Compounds as Potential Antifungals to Overcome the Emergence of Multidrug-Resistant Fungi

“…Fluvastatin, rosuvastatin, atorvastatin and simvastatin are statins used to lower the synthesis of cholesterol by inhibiting HMG-CoA. Statins may be an important adjuvant for the treatment of fungal infections because their efficiency has been reported against fungi, even against azole-resistant yeasts [65,92]. Indeed, Macreadie et al demonstrated a strong inhibition of the growth of Candida spp.…”

Overview of Emulgel as Emergent Topical Delivery: Recent Applications and Advancement

“…Clinical studies recorded significant enhancement in therapeutic response of MTD from optimized SLNs vaginal emulgel formulation regarding the clinical treatment and low recurrence rate against the marketed product. De Oliveira Neto AS et al [50], formulated atorvastatin loaded oral and vaginal emulgels and evaluated the antifungal activity of atorvastatin and concluded that atorvastatin emulgels could be utilized in treatment offungal infection. Golshah A, et al [51], investigated the gingivitis effectiveness of Resveratrol emulgel in orthodontic patients and found that the prepared Emulgel was effective in improving gingival health in orthodontic patients and in lowering…”