{"title":"用于治疗细胞内耐甲氧西林金黄色葡萄球菌感染的抗生素负载纳米粒子:一种新型抗生素的体外和体内疗效。","authors":"","doi":"10.1016/j.jconrel.2024.08.029","DOIUrl":null,"url":null,"abstract":"<div><p>Antimicrobial resistance is considered one of the biggest threats to public health worldwide. Methicillin-resistant <em>S. aureus</em> is the causative agent of a number of infections and lung colonization in people suffering from cystic fibrosis. Moreover, a growing body of evidence links the microbiome to the development of cancer, as well as to the success of the treatment. In this view, the development of novel antibiotics is of critical importance, and SV7, a novel antibiotic active against MRSA at low concentrations, represents a promising candidate. However, the low aqueous solubility of SV7 hampers its therapeutic translation. In this study, SV7 was encapsulated in poly(lactic-<em>co</em>-glycolic acid) (PLGA) nanoparticles (NPs) to improve the solubility profile, to ensure sustained release and eventually support deposition in the airways. Furthermore, PLGA NPs were formulated as dry powder to extend their shelf-life and were shown to efficiently target intracellular infections. After identifying a formulation with suitable physico-chemical characteristics, SV7-loaded NPs were investigated <em>in vitro</em> in terms of inhibitory activity against MRSA, and their safety profile in lung epithelial cells. Subsequently, the activity against MRSA intracellular infections was investigated in a co-culture model of MRSA and macrophages. To test the translatability of our findings, SV7-loaded NPs were tested <em>in vivo</em> in a <em>Galleria mellonella</em> infection model. In conclusion, SV7-loaded NPs showed a safe profile and efficient inhibitory activity against MRSA at low concentrations. Furthermore, their activity against intracellular infections was confirmed, and was retained <em>in vivo</em>, rendering them a promising candidate for treatment of MRSA lung infections.</p></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":null,"pages":null},"PeriodicalIF":10.5000,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0168365924005777/pdfft?md5=3d8e0fe99153b56a95b4ce971aa7c988&pid=1-s2.0-S0168365924005777-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Antibiotic-loaded nanoparticles for the treatment of intracellular methicillin-resistant Staphylococcus Aureus infections: In vitro and in vivo efficacy of a novel antibiotic\",\"authors\":\"\",\"doi\":\"10.1016/j.jconrel.2024.08.029\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Antimicrobial resistance is considered one of the biggest threats to public health worldwide. Methicillin-resistant <em>S. aureus</em> is the causative agent of a number of infections and lung colonization in people suffering from cystic fibrosis. Moreover, a growing body of evidence links the microbiome to the development of cancer, as well as to the success of the treatment. In this view, the development of novel antibiotics is of critical importance, and SV7, a novel antibiotic active against MRSA at low concentrations, represents a promising candidate. However, the low aqueous solubility of SV7 hampers its therapeutic translation. In this study, SV7 was encapsulated in poly(lactic-<em>co</em>-glycolic acid) (PLGA) nanoparticles (NPs) to improve the solubility profile, to ensure sustained release and eventually support deposition in the airways. Furthermore, PLGA NPs were formulated as dry powder to extend their shelf-life and were shown to efficiently target intracellular infections. After identifying a formulation with suitable physico-chemical characteristics, SV7-loaded NPs were investigated <em>in vitro</em> in terms of inhibitory activity against MRSA, and their safety profile in lung epithelial cells. Subsequently, the activity against MRSA intracellular infections was investigated in a co-culture model of MRSA and macrophages. To test the translatability of our findings, SV7-loaded NPs were tested <em>in vivo</em> in a <em>Galleria mellonella</em> infection model. In conclusion, SV7-loaded NPs showed a safe profile and efficient inhibitory activity against MRSA at low concentrations. Furthermore, their activity against intracellular infections was confirmed, and was retained <em>in vivo</em>, rendering them a promising candidate for treatment of MRSA lung infections.</p></div>\",\"PeriodicalId\":15450,\"journal\":{\"name\":\"Journal of Controlled Release\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.5000,\"publicationDate\":\"2024-08-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0168365924005777/pdfft?md5=3d8e0fe99153b56a95b4ce971aa7c988&pid=1-s2.0-S0168365924005777-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Controlled Release\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168365924005777\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Controlled Release","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168365924005777","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Antibiotic-loaded nanoparticles for the treatment of intracellular methicillin-resistant Staphylococcus Aureus infections: In vitro and in vivo efficacy of a novel antibiotic
Antimicrobial resistance is considered one of the biggest threats to public health worldwide. Methicillin-resistant S. aureus is the causative agent of a number of infections and lung colonization in people suffering from cystic fibrosis. Moreover, a growing body of evidence links the microbiome to the development of cancer, as well as to the success of the treatment. In this view, the development of novel antibiotics is of critical importance, and SV7, a novel antibiotic active against MRSA at low concentrations, represents a promising candidate. However, the low aqueous solubility of SV7 hampers its therapeutic translation. In this study, SV7 was encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to improve the solubility profile, to ensure sustained release and eventually support deposition in the airways. Furthermore, PLGA NPs were formulated as dry powder to extend their shelf-life and were shown to efficiently target intracellular infections. After identifying a formulation with suitable physico-chemical characteristics, SV7-loaded NPs were investigated in vitro in terms of inhibitory activity against MRSA, and their safety profile in lung epithelial cells. Subsequently, the activity against MRSA intracellular infections was investigated in a co-culture model of MRSA and macrophages. To test the translatability of our findings, SV7-loaded NPs were tested in vivo in a Galleria mellonella infection model. In conclusion, SV7-loaded NPs showed a safe profile and efficient inhibitory activity against MRSA at low concentrations. Furthermore, their activity against intracellular infections was confirmed, and was retained in vivo, rendering them a promising candidate for treatment of MRSA lung infections.
期刊介绍:
The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System.
Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries.
Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.