Kaltschmidt Bernhard P, Ennen Inga, Greiner Johannes F W, Dietsch Robin, Patel Anant, Kaltschmidt Barbara, Kaltschmidt Christian, Hütten Andreas
Thin Films & Physics of Nanostructures, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.
Department of Cell Biology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.
Biomedicines. 2020 May 1;8(5):105. doi: 10.3390/biomedicines8050105.
Terpenoids are natural plant-derived products that are applied to treat a broad range of human diseases, such as airway infections and inflammation. However, pharmaceutical applications of terpenoids against bacterial infection remain challenging due to their poor water solubility. Here, we produce invasomes encapsulating thymol, menthol, camphor and 1,8-cineol, characterize them via cryo transmission electron microscopy and assess their bactericidal properties. While control- and cineol-invasomes are similarly distributed between unilamellar and bilamellar vesicles, a shift towards unilamellar invasomes is observable after encapsulation of thymol, menthol or camphor. Thymol- and camphor-invasomes show a size reduction, whereas menthol-invasomes are enlarged and cineol-invasomes remain unchanged compared to control. While thymol-invasomes lead to the strongest growth inhibition of , camphor- or cineol-invasomes mediate cell death and growth is not affected by menthol-invasomes. Flow cytometric analysis validate that invasomes comprising thymol are highly bactericidal to . Notably, treatment with thymol-invasomes does not affect survival of Gram-negative In summary, we successfully produce terpenoid-invasomes and demonstrate that particularly thymol-invasomes show a strong selective activity against Gram-positive bacteria. Our findings provide a promising approach to increase the bioavailability of terpenoid-based drugs and may be directly applicable for treating severe bacterial infections such as methicillin-resistant .
萜类化合物是天然的植物衍生产品,可用于治疗多种人类疾病,如气道感染和炎症。然而,由于其水溶性差,萜类化合物在抗细菌感染的药物应用方面仍然具有挑战性。在此,我们制备了包裹百里香酚、薄荷醇、樟脑和1,8-桉叶素的侵入体,通过冷冻透射电子显微镜对其进行表征,并评估其杀菌特性。虽然对照侵入体和桉叶素侵入体在单层和双层囊泡之间的分布相似,但在包裹百里香酚、薄荷醇或樟脑后,可观察到向单层侵入体的转变。与对照相比,百里香酚和樟脑侵入体的尺寸减小,而薄荷醇侵入体增大,桉叶素侵入体保持不变。虽然百里香酚侵入体对[具体细菌名称未给出]的生长抑制作用最强,但樟脑或桉叶素侵入体介导细胞死亡,而薄荷醇侵入体对[具体细菌名称未给出]的生长没有影响。流式细胞术分析证实,包含百里香酚的侵入体对[具体细菌名称未给出]具有高度杀菌作用。值得注意的是,用百里香酚侵入体处理不会影响革兰氏阴性菌[具体细菌名称未给出]的存活。总之,我们成功制备了萜类化合物侵入体,并证明特别是百里香酚侵入体对革兰氏阳性菌具有强大的选择性活性。我们的研究结果为提高基于萜类化合物的药物的生物利用度提供了一种有前景的方法,并且可能直接适用于治疗严重细菌感染,如耐甲氧西林的[具体细菌名称未给出]。
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