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
{"title":"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","authors":"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","doi":"10.1016/j.nano.2023.102731","DOIUrl":null,"url":null,"abstract":"<div><p>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 <em>Galleria mellonella</em> larvae infection model.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963423000825/pdfft?md5=6d7933ff6822d44856d4b5da0e044201&pid=1-s2.0-S1549963423000825-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Improved pharmacokinetics and enhanced efficacy of the vancomycin derivative FU002 using a liposomal nanocarrier\",\"authors\":\"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\",\"doi\":\"10.1016/j.nano.2023.102731\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 <em>Galleria mellonella</em> larvae infection model.</p></div>\",\"PeriodicalId\":19050,\"journal\":{\"name\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2023-12-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1549963423000825/pdfft?md5=6d7933ff6822d44856d4b5da0e044201&pid=1-s2.0-S1549963423000825-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1549963423000825\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine : nanotechnology, biology, and medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1549963423000825","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
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.
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.