Nanoemulsões de óleo essencial de Baccharis dracunculifolia: desenvolvimento, caracterização e potencial para cicatrização da pele

Abstract

Alkyl polyglucosides (APG) are nonionic surfactants derived from renewable sources, with favorable ecotoxicological properties and high biodegradability, making them attractive for the development of safe and sustainable pharmaceutical formulations. The essential oil of Baccharis dracunculifolia (BDO), rich in bioactive compounds such as β-caryophyllene and t-nerolidol, possesses antimicrobial and anti-inflammatory properties, granting it potential for topical applications aimed at wound healing. In this context, this study aimed to develop an innovative polyethylene glycol (PEG)-free nanoemulsion using an APG surfactant to encapsulate BDO, characterizing its stability, physicochemical properties, and potential safety. Additionally, the study investigated the pH-dependent behavior of APG surfactants and their influence on the stability and uniformity of nanoemulsions, an aspect scarcely explored in pharmaceutical science to date. This study also analyzed the contents of t-nerolidol and β-caryophyllene in BDO, evaluated its toxicity in human fibroblast cells, and assessed its effect on cell migration. High-performance liquid chromatography (HPLC) analysis revealed the presence of 13.84% t-nerolidol and 2.68% β-caryophyllene in the essential oil. Cytotoxicity tests showed that BDO exhibited no toxicity up to concentrations of 500 μg/mL, and cell migration assays demonstrated its potential for wound healing, with wound closure rates significantly higher than the control: approximately 71% and 78% at 24 and 48 hours, respectively, compared to 43% and 51% in the same intervals, indicating its potential for skin repair. Through the construction of a ternary phase diagram, four formulations were selected and processed by ultrasound, resulting in the translucent appearance characteristic of nanometric colloidal suspensions. The formulations were evaluated for mean hydrodynamic droplet diameter, polydispersity index (PdI), zeta potential (ZP), and conductivity over 90 days. Nanoemulsions prepared with a surfactant:BDO ratio of 1:1 produced droplets smaller than 60 nm with low polydispersity (PdI < 0.2). The initial pH of the formulations was high (pH > 11) due to the APG. After adjustments to pH 6.5, an increase in droplet size to 78 nm and PdI to 0.3 was observed, suggesting alterations in the interfacial activity of the surfactant. After 90 days, the nanoemulsion at pH 6.5 stabilized with a droplet size of approximately 120 nm and PdI < 0.3, indicating a monodisperse system. Conversely, the nanoemulsion at pH 11.5 exhibited early instability, with PdI > 0.3 after 21 days, suggesting coalescence. Spectroscopic analyses confirmed conformational changes in the APG and BDO related to pH variations, supporting the hypothesis of pH-dependent conformational changes in APG. Moreover, the HET-CAM test indicated a lower irritation score (IS 3.0 ± 0.0) for the nanoemulsion at pH 6.5 compared to pH 11.5 (IS 3.6 ± 1.15), reinforcing the importance of pH control for the safety of topical formulations. This work highlights the potential of APG-based nanoemulsions for safer and more sustainable pharmaceutical products, emphasizing the pH-sensitive behavior of this system.