Tat-functionalized liposomes for the treatment of meningitis: an in vitro study

Caterina Bartomeu Garcia,1,* Di Shi,2,* Thomas J Webster2 1Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA *These authors contributed equally to this work Abstract: Bacterial meningit...

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Autores principales:	Bartomeu Garcia C, Shi D, Webster TJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	fusogenic liposomes cell penetrating peptides minimum inhibitory concentration (MIC) bacteria colony forming units fluorescence microscopy cytotoxicity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a543060a4b514191baed1bffde575665
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spelling	oai:doaj.org-article:a543060a4b514191baed1bffde5756652021-12-02T00:37:18ZTat-functionalized liposomes for the treatment of meningitis: an in vitro study1178-2013https://doaj.org/article/a543060a4b514191baed1bffde5756652017-04-01T00:00:00Zhttps://www.dovepress.com/tat-functionalized-liposomes-for-the-treatment-of-meningitis-an-in-vit-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Caterina Bartomeu Garcia,1,* Di Shi,2,* Thomas J Webster2 1Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA *These authors contributed equally to this work Abstract: Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47–57, which is a peptide derived from the Tat protein of HIV). The purpose of this in vitro study was to demonstrate for the first time the ability of the presently prepared fusogenic liposomes, which were spherical particles with a diameter of 100 nm loaded with antibiotics and functionalized with-cell penetrating peptides (Tat47–57), to fight the main bacteria that cause meningitis. For this, vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic liposomes to fight Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Antibacterial activity of Tat-functionalized and nonfunctionalized liposomes loaded with antibiotics was tested by determining bacteria colony-forming units and growth-curve assays coupled with live/dead assays using fluorescence microscopy. Results showed a remarkable decrease in antibiotic minimum inhibitory concentration when all of the bacteria were treated with these novel liposomes, especially for the functionalized liposomes loaded with methicillin. With antibiotic concentrations of 1.7–3 µg/mL for Tat-functionalized liposomes loaded with methicillin, the bacteria population was totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells, major cellular components of the blood–brain barrier, were also performed for all of the liposomes, including free antibiotic and the Tat peptide. Results showed much promise for the further study of the presently formulated liposomes to treat meningitis. Keywords: fusogenic liposomes, cell-penetrating peptides, minimum inhibitory concentration, MIC, bacteria colony-forming units, fluorescence microscopy, cytotoxicityBartomeu Garcia CShi DWebster TJDove Medical Pressarticlefusogenic liposomescell penetrating peptidesminimum inhibitory concentration (MIC)bacteria colony forming unitsfluorescence microscopycytotoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3009-3021 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	fusogenic liposomes cell penetrating peptides minimum inhibitory concentration (MIC) bacteria colony forming units fluorescence microscopy cytotoxicity Medicine (General) R5-920
spellingShingle	fusogenic liposomes cell penetrating peptides minimum inhibitory concentration (MIC) bacteria colony forming units fluorescence microscopy cytotoxicity Medicine (General) R5-920 Bartomeu Garcia C Shi D Webster TJ Tat-functionalized liposomes for the treatment of meningitis: an in vitro study
description	Caterina Bartomeu Garcia,1,* Di Shi,2,* Thomas J Webster2 1Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, Spain; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA *These authors contributed equally to this work Abstract: Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47–57, which is a peptide derived from the Tat protein of HIV). The purpose of this in vitro study was to demonstrate for the first time the ability of the presently prepared fusogenic liposomes, which were spherical particles with a diameter of 100 nm loaded with antibiotics and functionalized with-cell penetrating peptides (Tat47–57), to fight the main bacteria that cause meningitis. For this, vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic liposomes to fight Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Antibacterial activity of Tat-functionalized and nonfunctionalized liposomes loaded with antibiotics was tested by determining bacteria colony-forming units and growth-curve assays coupled with live/dead assays using fluorescence microscopy. Results showed a remarkable decrease in antibiotic minimum inhibitory concentration when all of the bacteria were treated with these novel liposomes, especially for the functionalized liposomes loaded with methicillin. With antibiotic concentrations of 1.7–3 µg/mL for Tat-functionalized liposomes loaded with methicillin, the bacteria population was totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells, major cellular components of the blood–brain barrier, were also performed for all of the liposomes, including free antibiotic and the Tat peptide. Results showed much promise for the further study of the presently formulated liposomes to treat meningitis. Keywords: fusogenic liposomes, cell-penetrating peptides, minimum inhibitory concentration, MIC, bacteria colony-forming units, fluorescence microscopy, cytotoxicity
format	article
author	Bartomeu Garcia C Shi D Webster TJ
author_facet	Bartomeu Garcia C Shi D Webster TJ
author_sort	Bartomeu Garcia C
title	Tat-functionalized liposomes for the treatment of meningitis: an in vitro study
title_short	Tat-functionalized liposomes for the treatment of meningitis: an in vitro study
title_full	Tat-functionalized liposomes for the treatment of meningitis: an in vitro study
title_fullStr	Tat-functionalized liposomes for the treatment of meningitis: an in vitro study
title_full_unstemmed	Tat-functionalized liposomes for the treatment of meningitis: an in vitro study
title_sort	tat-functionalized liposomes for the treatment of meningitis: an in vitro study
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/a543060a4b514191baed1bffde575665
work_keys_str_mv	AT bartomeugarciac tatfunctionalizedliposomesforthetreatmentofmeningitisaninvitrostudy AT shid tatfunctionalizedliposomesforthetreatmentofmeningitisaninvitrostudy AT webstertj tatfunctionalizedliposomesforthetreatmentofmeningitisaninvitrostudy
_version_	1718403637446705152

Tat-functionalized liposomes for the treatment of meningitis: an in vitro study

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