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与氟康唑共包封于纳米结构脂质载体中的定制一锅法多组分单萜的协同和潜在抗真菌特性。

Synergistic and potential antifungal properties of tailored, one pot multicomponent monoterpenes co-delivered with fluconazole encapsulated nanostructure lipid carrier.

机构信息

Supplementary General Sciences Department, Faculty of Oral and Dental Medicine, Future University in Egypt, Cairo, 11835, Egypt.

Center for Materials Science (CMS), Zewail City of Science and Technology, 6th of October, Giza, 12578, Egypt.

出版信息

Sci Rep. 2024 Jun 22;14(1):14382. doi: 10.1038/s41598-024-63149-x.

Abstract

Frequent and variant infections are caused by the virtue of opportunistic fungi pathogens. Candidiasis, aspergillosis, and mucormycosis are pathogenic microorganisms that give rise to vast fungal diseases that alternate between moderate to fatal in severity. The use of fluconazole as an antifungal drug was limited due to the acquired resistance in some types of Candida and other fungal species. This study aims to consolidate fluconazole's biological effectiveness against several pathogenic fungi. Six active monoterpenes (MTs) of carvacrol, linalool, geraniol, α-terpinene, citronellal, and nerolidol were selected and encapsulated in nanostructure lipid carrier (NLC) with (NLC-Flu-MTs) and/without (NLC-MTs) fluconazole in one nanoformulation to determine if they will act synergistically or not? The synthesized nanoformulation NLC-Flu-MTs and NLC-MTs exhibited very good particle size of 144.5 nm and 138.6 nm for size and zeta potential values of (- 23.5 mV) and (- 20.3 mV), respectively. Transmission electron microscope investigation confirmed that the synthesized NLCs have regular and spherical shape. The abundance and concentration of the six released monoterpenes were determined, as a novel approach, using GC-MS with very good results and validity. In-vitro antifungal screening was done before and after nano co-delivery against seven pathogenic, and aggressive fungi of Candida tropicalis, Candida krusei, Candida glabrata, Geotrichum Candidum, Candidaalbicans, Aspergillus Niger, and mucor circinelloides. Inhibition Zone diameter (IZD) and the minimum inhibitory concentration (MIC) were measured. Nanoformulations NLC-Flu-MTs and NLC-MTs manifested potential and unique biological susceptibility against all the tested microorganisms with reduced (MIC) values, especially against Candida Tropicalis (MIC = 0.97 µg/ml) which represents 16-fold of the value shown by NLC-MTs (MIC = 15.6 µg/ml) and 64-fold of fluconazole free before nanoformulation (MIC = 62.5 µg/ml). The efficiency of nanomaterials, particularly NLC-Flu-MTs, has become evident in the diminishing value of MIC which affirmed the synergism between fluconazole and the other six monoterpenes.

摘要

频繁和多样的感染是由机会性真菌病原体引起的。念珠菌病、曲霉菌病和毛霉菌病是引起广泛真菌感染的致病微生物,这些感染的严重程度从中度到致命不等。氟康唑作为一种抗真菌药物的使用受到限制,因为某些类型的念珠菌和其他真菌物种已经产生了耐药性。本研究旨在综合氟康唑对几种致病性真菌的生物学有效性。选择了香芹酚、芳樟醇、香叶醇、α-松油烯、柠檬醛和橙花叔醇这 6 种活性单萜(MTs),并将其封装在纳米结构脂质载体(NLC)中,制成(NLC-Flu-MTs)和/或不包含(NLC-MTs)氟康唑的一种纳米制剂,以确定它们是否具有协同作用?合成的纳米制剂 NLC-Flu-MTs 和 NLC-MTs 的粒径分别为 144.5nm 和 138.6nm,Zeta 电位值分别为(-23.5mV)和(-20.3mV)。透射电子显微镜研究证实,所合成的 NLC 具有规则的球形形态。采用 GC-MS 法测定了 6 种单萜的释放量和浓度,结果非常好,具有很好的有效性。在纳米共递药之前和之后,对七种致病性和侵袭性真菌(热带念珠菌、克柔念珠菌、光滑念珠菌、近平滑念珠菌、白色念珠菌、黑曲霉和卷枝毛霉)进行了体外抗真菌筛选。测量抑菌圈直径(IZD)和最小抑菌浓度(MIC)。纳米制剂 NLC-Flu-MTs 和 NLC-MTs 对所有测试的微生物均表现出潜在的独特的生物敏感性,MIC 值降低,特别是对热带念珠菌(MIC=0.97μg/ml),其值比 NLC-MTs(MIC=15.6μg/ml)低 16 倍,比纳米制剂前未包裹氟康唑(MIC=62.5μg/ml)低 64 倍。纳米材料,特别是 NLC-Flu-MTs 的效率在 MIC 值的降低中得到了证明,这证实了氟康唑和其他六种单萜之间的协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/015a/11193721/d8939c152e99/41598_2024_63149_Fig1_HTML.jpg

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