Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes.

Terbinafine hydrochloride is a synthetic allylamine whose mechanism of action consists of inhibiting the enzyme squalene epoxidase that participates in the first stage of ergosterol synthesis, interfering with fungal membrane function. Ozonated oils are used for topical application of ozone, producing reactive oxygen species that cause cellular damage in microorganisms, therefore being an alternative treatment for acute and chronic skin infections. This study aimed to develop and characterize Eudragit® RS100 nanocapsules, obtained by interfacial deposition of preformed polymer method, containing 0.5% terbinafine hydrochloride and 5% ozonated sunflower seed oil as a potential treatment against dermatophytes. The polymeric nanocapsules were characterized regarding particle size, zeta potential, pH, drug content, encapsulation efficiency, and stability. The in vitro drug release, in vitro skin permeation, and in vitro antifungal activity were also evaluated. The particle size was around 150 nm with a narrow size distribution, the zeta potential was around + 6 mV, and the pH was 2.2. The drug content was close to 95% with an encapsulation efficiency of 53%. The nanocapsules were capable to control the drug release and the skin permeation. The in vitro susceptibility test showed greater antifungal activity for the developed nanocapsules, against all dermatophyte strains tested, compared to the drug solution. Therefore, the polymeric nanocapsules suspension containing terbinafine hydrochloride and ozonated oil can be considered a potential high-efficacy candidate for the treatment of dermatophytosis, with a possible reduction in the drug dose and frequency of applications. Studies to evaluate safety and efficacy in vivo still need to be performed.

Effectiveness and Safety of Ozone Therapy for Dermatological Disorders: A Literature Review of Clinical Trials.

Ozone is a strong oxidizing agent, capable of promoting therapeutic effects such as antimicrobial, anti inflammatory, antioxidant and healing activities, with low probability of toxicity when used in a specific dosage range. The aim of this study was to conduct a literature review to assess clinical trials available over the past 10 years regarding the effectiveness and safety of ozone therapy to treat dermatological disorders. The search for bibliographic material was carried out through PubMed, Cochrane Library and Google Scholar electronic databases. The inclusion criteria covered only controlled clinical trials published from 2011 to 2021 and written in English. The 18 selected clinical trials included 1279 patients (ranging from 12 to 400 patients per study), of which 1185 patients were adults and 94 were children. Ozone therapy was evaluated regarding the treatment of diabetic foot ulcers, digital ulcers, chronic venous leg ulcers, atopic dermatitis, skin burns, onychomycosis, tinea pedis, cutaneous leishmaniasis, balanitis xerotica obliterans and multiple common warts. Only three studies, addressing the treatment of cutaneous leishmaniasis, skin ulcers and skin burns, evidenced lack of effectiveness of ozone treatment. Mild adverse effects occurred in three clinical trials, whereas severe side effects occurred in only one clinical trial, regarding skin ulcers. Therefore, ozone therapy may be suggested as an alternative or complementary treatment in some types of dermatological conditions specially affecting refractory patients. Though, a greater number of high-quality clinical trials is needed to clearly establish the safety of ozone therapy in dermatological disorders.