利用脂质体纳米载体改善万古霉素衍生物 FU002 的药代动力学并提高其疗效

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Julia Werner MSc , Florian Umstätter PhD , Tobias Hertlein PhD , Barbro Beijer PhD , Christian Kleist PhD , Eric Mühlberg MSc , Stefan Zimmermann MD , Uwe Haberkorn MD , Knut Ohlsen PhD , Gert Fricker PhD , Walter Mier PhD , Philipp Uhl PhD
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引用次数: 0

摘要

抗生素耐药性仍然是一个全球健康问题,它削弱了有效抗生素的储备。最近,我们报道了万古霉素衍生物 FU002,它是一种对革兰氏阳性细菌非常有效的物质,具有克服万古霉素耐药性的潜力。然而,由于 FU002 能迅速从血流中排出,因此无法将其出色的抗菌活性转化为临床疗效。为了改善其药代动力学,我们将 FU002 封装在 PEG 脂质体中。PEG 脂质体 FU002 对肝、肾和红细胞没有相关的细胞毒性。对 Wistar 大鼠的研究表明,脂质体抗生素的血液循环时间明显延长。在微量稀释试验中,可以证明脂质体不会降低对葡萄球菌和肠球菌的抗菌活性。与游离态相比,脂质体 FU002 在灰飞虱幼虫感染模型中表现出更高的疗效,这凸显了其强大的功效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Improved pharmacokinetics and enhanced efficacy of the vancomycin derivative FU002 using a liposomal nanocarrier

Improved pharmacokinetics and enhanced efficacy of the vancomycin derivative FU002 using a liposomal nanocarrier

Improved pharmacokinetics and enhanced efficacy of the vancomycin derivative FU002 using a liposomal nanocarrier

Antibiotic resistance still represents a global health concern which diminishes the pool of effective antibiotics. With the vancomycin derivative FU002, we recently reported a highly potent substance active against Gram-positive bacteria with the potential to overcome vancomycin resistance. However, the translation of its excellent antimicrobial activity into clinical efficiency could be hampered by its rapid elimination from the blood stream. To improve its pharmacokinetics, we encapsulated FU002 in PEGylated liposomes. For PEG-liposomal FU002, no relevant cytotoxicity on liver, kidney and red blood cells was observed. Studies in Wistar rats revealed a significantly prolonged blood circulation of the liposomal antibiotic. In microdilution assays it could be demonstrated that encapsulation does not diminish the antimicrobial activity against staphylococci and enterococci. Highlighting its great potency, liposomal FU002 exhibited a superior therapeutic efficacy when compared to the free form in a Galleria mellonella larvae infection model.

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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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