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氧化锌纳米颗粒的两性霉素B-聚乙二醇缀合物:增强抗真菌活性并将毒性降至最低

Amphotericin B-PEG Conjugates of ZnO Nanoparticles: Enhancement Antifungal Activity with Minimal Toxicity.

作者信息

Alshahrani Saad M, Khafagy El-Sayed, Riadi Yassine, Al Saqr Ahmed, Alfadhel Munerah M, Hegazy Wael A H

机构信息

Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

出版信息

Pharmaceutics. 2022 Aug 7;14(8):1646. doi: 10.3390/pharmaceutics14081646.

Abstract

Amphotericin B (AMB) is commonly used to treat life-threatening systemic fungal infections. AMB formulations that are more efficient and less nephrotoxic are currently unmet needs. In the current study, new ZnO-PEGylated AMB (ZnO-AMB-PEG) nanoparticles (NPs) were synthesized and their antifungal effects on the spp. were investigated. The size and zeta potential values of AMB-PEG and ZnO-AMB-PEG NPs were 216.2 ± 26.9 to 662.3 ± 24.7 nm and -11.8 ± 2.02 to -14.2 ± 0.94 mV, respectively. The FTIR, XRD, and EDX spectra indicated that the PEG-enclosed AMB was capped by ZnO, and SEM images revealed the ZnO distribution on the surface NPs. In comparison to ZnO-AMB NPs and free AMB against and , ZnO-AMB-PEG NPs significantly reduced the MIC and MFC. After a week of single and multiple dosage, the toxicity was investigated utilizing in vitro blood hemolysis, in vivo nephrotoxicity, and hepatic functions. ZnO-AMB-PEG significantly lowered WBC count and hematocrit concentrations when compared to AMB and ZnO-AMB. RBC count and hemoglobulin content, on the other hand, were unaltered. ZnO-AMB-PEG considerably lowered creatinine and blood urea nitrogen (BUN) levels when compared to AMB and ZnO-AMB. The difference in liver function indicators was determined to be minor by all formulae. These findings imply that ZnO-AMB-PEG could be utilized in the clinic with little nephrotoxicity, although more research is needed to determine the formulation's in vivo efficacy.

摘要

两性霉素B(AMB)常用于治疗危及生命的全身性真菌感染。目前,更高效且肾毒性更低的AMB制剂仍未得到满足。在本研究中,合成了新型的ZnO-聚乙二醇化两性霉素B(ZnO-AMB-PEG)纳米颗粒(NPs),并研究了它们对[具体菌种]的抗真菌作用。AMB-PEG和ZnO-AMB-PEG NPs的粒径和zeta电位值分别为216.2±26.9至662.3±24.7nm和-11.8±2.02至-14.2±0.94mV。傅里叶变换红外光谱(FTIR)、X射线衍射(XRD)和能谱分析(EDX)表明,包裹聚乙二醇的AMB被ZnO覆盖,扫描电子显微镜(SEM)图像显示了ZnO在纳米颗粒表面的分布。与ZnO-AMB NPs和游离AMB相比,ZnO-AMB-PEG NPs对[具体菌种1]和[具体菌种2]显著降低了最低抑菌浓度(MIC)和最低杀菌浓度(MFC)。单次和多次给药一周后,利用体外血液溶血、体内肾毒性和肝功能研究毒性。与AMB和ZnO-AMB相比,ZnO-AMB-PEG显著降低了白细胞计数和血细胞比容浓度。另一方面,红细胞计数和血红蛋白含量未改变。与AMB和ZnO-AMB相比,ZnO-AMB-PEG显著降低了肌酐和血尿素氮(BUN)水平。所有配方对肝功能指标的差异均较小。这些发现表明,ZnO-AMB-PEG可能在临床上以低肾毒性使用,尽管需要更多研究来确定该制剂的体内疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a47/9415822/6ec35c5b8569/pharmaceutics-14-01646-g001.jpg

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