<scp>PEG</scp>‐Free Nanoemulsions With Alkyl Polyglucoside and <i>Baccharis dracunculifolia</i> Essential Oil: Physicochemical Behavior, <scp>pH</scp> Dependence and Skin Repair Properties

ABSTRACT Alkyl polyglucosides (APG) are biodegradable, non‐ionic surfactants from renewable sources with low ecotoxicity. This study developed a novel PEG‐free nanoemulsion (NE) using APG to encapsulate Baccharis dracunculifolia essential oil (BDO) for skin repair. Cytotoxicity tests suggested no toxicity for BDO up to 500 μg/mL, and BDO significantly enhanced skin cell migration, indicating potential for skin repair. NEs (1:1 surfactant:BDO) had droplets &lt; 60 nm and low polydispersity (PdI &lt; 0.2). Preliminary NEs had pH &gt; 11, attributed to APG, but adjusting to 6.5 increased droplet size (78 nm) and PdI to 0.3 due to APG interfacial activity changes. After 90 days, NE at pH 6.5 stabilized (~120 nm, PdI &lt; 0.3), indicating a monodisperse system. Conversely, NE at pH 11.5 had a PdI &gt; 0.3 after 21 days, suggesting coalescence. Spectroscopic analyses revealed structural changes in APG and BDO linked to pH variations, supporting the hypothesis of pH‐dependent conformational changes in APG. The HET‐CAM test indicated a lower irritation score (IS 3.0 ± 0.0) for NE at pH 6.5 vs. 11.5 (IS 3.6 ± 1.15), corroborating the importance of pH adjustment for safe topical applications. This study highlights APG‐based NEs as promising for pharmaceuticals and cosmetics, emphasizing the need to further explore APG's pH‐sensitive behavior.