Gil Gabriela Alberto, Kakuda Letícia, Tonani Ludmilla, von Zeska Kress Marcia Regina, Oliveira Wanderley Pereira
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-903, Brazil.
ACS Omega. 2025 Feb 20;10(8):7876-7887. doi: 10.1021/acsomega.4c08578. eCollection 2025 Mar 4.
In recent decades, the recurrence and mortality rates of fungal infections have increased, likely due to antifungal resistance and insufficient attention from healthcare authorities. This trend highlights the urgent need for new antifungal treatments, with essential oils (EOs) emerging as promising alternatives. This study focuses on the characterization, nanoencapsulation, and evaluation of the EO of Kunth - pepper-rosemary - on toxicity and antifungal activity against filamentous fungi and yeasts, with a particular emphasis on the influence of surfactants. The EO was characterized by GC-MS and encapsulated in Nanostructured Lipid Carriers (NLCs) using either a nonionic surfactant or a combination with a cationic surfactant. NLCs were further characterized by the determination of the retention of the marker compound by high-performance liquid chromatography (HPLC), of morphology by transmission electronic microscopy (TEM), and their stability was assessed under thermal stress over 28 days. Minimum inhibitory concentrations (MIC) were determined against four yeast fungi - (ATCC 64548), (CDC B11903), (ATCC 22019), and (ATCC 14521) - and three filamentous fungi - (ATCC 204304), (ATCC 36031), and (ATCC 28188). The NLC's acute toxicity was evaluated in larvae. The results demonstrated the stability, safety, and potent antifungal efficacy of EO-loaded NLCs. The charge of the NLCs played a critical role in their antifungal performance for most fungal species. The differential responses observed suggest that CTAB enhances antifungal activity by imparting a positive charge to the nanoparticles, creating an additive effect with thymol. CTAB's ability to reverse the fungal cell surface charge from negative to positive was significant. However, , , and showed no sensitivity to CTAB, indicating that surface charge was not a factor for these fungi. The EO and its NLC formulations exhibited significant in vitro antifungal activity, suggesting their potential as alternative therapies for fungal infections.
近几十年来，真菌感染的复发率和死亡率有所上升，这可能是由于抗真菌耐药性以及医疗当局的关注不足所致。这一趋势凸显了对新型抗真菌治疗的迫切需求，而精油（EOs）正成为有前景的替代方案。本研究聚焦于对昆特胡椒 - 迷迭香精油的表征、纳米包封，以及评估其对丝状真菌和酵母的毒性及抗真菌活性，特别强调表面活性剂的影响。通过气相色谱 - 质谱联用（GC-MS）对该精油进行表征，并使用非离子表面活性剂或与阳离子表面活性剂组合的方式将其包封于纳米结构脂质载体（NLCs）中。通过高效液相色谱（HPLC）测定标记化合物的保留率、透射电子显微镜（TEM）观察形态，对NLCs进行进一步表征，并在28天的热应激条件下评估其稳定性。测定了对四种酵母真菌——（美国典型培养物保藏中心64548）、（疾病控制与预防中心B11903）、（美国典型培养物保藏中心22019）和（美国典型培养物保藏中心14521）——以及三种丝状真菌——（美国典型培养物保藏中心204304）、（美国典型培养物保藏中心36031）和（美国典型培养物保藏中心28188）的最低抑菌浓度（MIC）。在幼虫中评估了NLCs的急性毒性。结果证明了负载精油的NLCs的稳定性、安全性和强效抗真菌功效。对于大多数真菌种类，NLCs的电荷在其抗真菌性能中起关键作用。观察到的不同反应表明，十六烷基三甲基溴化铵（CTAB）通过赋予纳米颗粒正电荷来增强抗真菌活性，与百里香酚产生协同效应。CTAB将真菌细胞表面电荷从负变为正的能力显著。然而，、和对CTAB不敏感，表明表面电荷对这些真菌不是一个影响因素。该精油及其NLC制剂表现出显著的体外抗真菌活性，表明它们作为真菌感染替代疗法的潜力。
