Pré-formulação de NE contendo Anfotericina B direcionada a via nose-to-brain para o tratamento de infecções fúngicas do Sistema Nervoso Central.

Abstract

The increase in fungal infection cases in the central nervous system, especially in immunosuppressed patients, has driven the search for more effective therapies. Amphotericin B (AmB), despite its potent antifungal action, presents low water solubility and high systemic toxicity, which limits its therapeutic use and reinforces the use of lipid systems to increase solubility and decrease toxicity. Nanoemulsions for nose-to-brain drug delivery have emerged as a promising alternative to enhance the local bioavailability of anti-infective agents. Accordingly, this work aimed to preformulate an Amphotericin B (AmB)-loaded nanoemulsion intended for nose-to-brain delivery. A pseudoternary phase diagram was constructed to provide the necessary composition of a nanoemulsion (NE). The conductivity of the chosen NE was evaluated. Additionally, the NE was stored in triplicate for 30 days at 4, 25, and 50 ºC, and its droplet size, polydispersity index, and zeta potential were periodically analyzed. Moreover, surface tension and morphology by transmission electronic microscopy were assessed. They corroborated the adequate characteristics of the NE. Finally, AmB was incorporated into the developed system, and its entrapment efficiency (EE %) was determined by a spectroscopic method. The NE was obtained and selected by the pseudoternary phase diagram. The conductivity study revealed an oil-in-water system, and the preliminary stability demonstrated that the system is stable at room temperature. The nanoemulsions containing AmB showed higher entrapment efficiency at 0.1 mg/mL and lower efficiency at 1.0 mg/mL, indicating a possible saturation of the system at high concentrations. From this, the results demonstrated the achievement of a stable NE at room temperature, which showed a high EE % of AmB at a concentration of 0.1 mg/mL, incorporating an average of 0.0953 mg/mL, highlighting the potential for optimization via the nose-to-brain route.