Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci

Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and system...

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Autores principales:	Anna Maria Schito, Debora Caviglia, Gabriella Piatti, Alessia Zorzoli, Danilo Marimpietri, Guendalina Zuccari, Gian Carlo Schito, Silvana Alfei
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	fourth-generation polyester-based lysine-modified dendrimer physical encapsulation ursolic acid (UA) Gram-positive MDR isolates MICs time-kill experiments Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/3436967a857744f1ae5bd23ef34b96b6
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spelling	oai:doaj.org-article:3436967a857744f1ae5bd23ef34b96b62021-11-25T18:42:37ZEfficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci10.3390/pharmaceutics131119761999-4923https://doaj.org/article/3436967a857744f1ae5bd23ef34b96b62021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1976https://doaj.org/toc/1999-4923Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and systemic toxicity limit the possibilities of its application in vivo. Consequently, the beneficial activities of UA observed in vitro lose their potential clinical relevance unless water-soluble, not cytotoxic UA formulations are developed. With a nano-technologic approach, we have recently prepared water-soluble UA-loaded dendrimer nanoparticles (UA-G4K NPs) non-cytotoxic on HeLa cells, with promising physicochemical properties for their clinical applications. In this work, with the aim of developing a new antibacterial agent based on UA, UA-G4K has been tested on different strains of the <i>Enterococcus</i> genus, including marine isolates, toward which UA-G4K has shown minimum inhibitory concentrations (MICs) very low (0.5–4.3 µM), regardless of their resistance to antibiotics. Time-kill experiments, in addition to confirming the previously reported bactericidal activity of UA against <i>E. faecium</i>, also established it for UA-G4K. Furthermore, cytotoxicity experiments on human keratinocytes revealed that nanomanipulation of UA significantly reduced the cytotoxicity of UA, providing UA-G4K NPs with very high LD<sub>50</sub> (96.4 µM) and selectivity indices, which were in the range 22.4–192.8, depending on the enterococcal strain tested. Due to its physicochemical and biological properties, UA-G4K could be seriously evaluated as a novel oral-administrable therapeutic option for tackling difficult-to-treat enterococcal infections.Anna Maria SchitoDebora CavigliaGabriella PiattiAlessia ZorzoliDanilo MarimpietriGuendalina ZuccariGian Carlo SchitoSilvana AlfeiMDPI AGarticlefourth-generation polyester-based lysine-modified dendrimerphysical encapsulationursolic acid (UA)Gram-positive MDR isolatesMICstime-kill experimentsPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1976, p 1976 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fourth-generation polyester-based lysine-modified dendrimer physical encapsulation ursolic acid (UA) Gram-positive MDR isolates MICs time-kill experiments Pharmacy and materia medica RS1-441
spellingShingle	fourth-generation polyester-based lysine-modified dendrimer physical encapsulation ursolic acid (UA) Gram-positive MDR isolates MICs time-kill experiments Pharmacy and materia medica RS1-441 Anna Maria Schito Debora Caviglia Gabriella Piatti Alessia Zorzoli Danilo Marimpietri Guendalina Zuccari Gian Carlo Schito Silvana Alfei Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci
description	Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and systemic toxicity limit the possibilities of its application in vivo. Consequently, the beneficial activities of UA observed in vitro lose their potential clinical relevance unless water-soluble, not cytotoxic UA formulations are developed. With a nano-technologic approach, we have recently prepared water-soluble UA-loaded dendrimer nanoparticles (UA-G4K NPs) non-cytotoxic on HeLa cells, with promising physicochemical properties for their clinical applications. In this work, with the aim of developing a new antibacterial agent based on UA, UA-G4K has been tested on different strains of the <i>Enterococcus</i> genus, including marine isolates, toward which UA-G4K has shown minimum inhibitory concentrations (MICs) very low (0.5–4.3 µM), regardless of their resistance to antibiotics. Time-kill experiments, in addition to confirming the previously reported bactericidal activity of UA against <i>E. faecium</i>, also established it for UA-G4K. Furthermore, cytotoxicity experiments on human keratinocytes revealed that nanomanipulation of UA significantly reduced the cytotoxicity of UA, providing UA-G4K NPs with very high LD<sub>50</sub> (96.4 µM) and selectivity indices, which were in the range 22.4–192.8, depending on the enterococcal strain tested. Due to its physicochemical and biological properties, UA-G4K could be seriously evaluated as a novel oral-administrable therapeutic option for tackling difficult-to-treat enterococcal infections.
format	article
author	Anna Maria Schito Debora Caviglia Gabriella Piatti Alessia Zorzoli Danilo Marimpietri Guendalina Zuccari Gian Carlo Schito Silvana Alfei
author_facet	Anna Maria Schito Debora Caviglia Gabriella Piatti Alessia Zorzoli Danilo Marimpietri Guendalina Zuccari Gian Carlo Schito Silvana Alfei
author_sort	Anna Maria Schito
title	Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci
title_short	Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci
title_full	Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci
title_fullStr	Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci
title_full_unstemmed	Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci
title_sort	efficacy of ursolic acid-enriched water-soluble and not cytotoxic nanoparticles against enterococci
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3436967a857744f1ae5bd23ef34b96b6
work_keys_str_mv	AT annamariaschito efficacyofursolicacidenrichedwatersolubleandnotcytotoxicnanoparticlesagainstenterococci AT deboracaviglia efficacyofursolicacidenrichedwatersolubleandnotcytotoxicnanoparticlesagainstenterococci AT gabriellapiatti efficacyofursolicacidenrichedwatersolubleandnotcytotoxicnanoparticlesagainstenterococci AT alessiazorzoli efficacyofursolicacidenrichedwatersolubleandnotcytotoxicnanoparticlesagainstenterococci AT danilomarimpietri efficacyofursolicacidenrichedwatersolubleandnotcytotoxicnanoparticlesagainstenterococci AT guendalinazuccari efficacyofursolicacidenrichedwatersolubleandnotcytotoxicnanoparticlesagainstenterococci AT giancarloschito efficacyofursolicacidenrichedwatersolubleandnotcytotoxicnanoparticlesagainstenterococci AT silvanaalfei efficacyofursolicacidenrichedwatersolubleandnotcytotoxicnanoparticlesagainstenterococci
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Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci

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