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Article

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

1
Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, 16132 Genoa, Italy
2
Stem Cell Laboratory and Cell Therapy Center, IRCCS Istituto Giannina Gaslini, via Gerolamo Gaslini 5, 16147 Genoa, Italy
3
Department of Pharmacy, University of Genoa, Viale Cembrano 4, 16148 Genoa, Italy
*
Author to whom correspondence should be addressed.
Academic Editors: Cristina Sánchez González, Juan Llopis and Lorenzo Rivas García
Pharmaceutics 2021, 13(11), 1976; https://doi.org/10.3390/pharmaceutics13111976
Received: 2 November 2021 / Revised: 17 November 2021 / Accepted: 18 November 2021 / Published: 21 November 2021
(This article belongs to the Special Issue New Trends in Therapy: From Natural Products to Nanomedicine)
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 Enterococcus 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 E. faecium, 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 LD50 (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. View Full-Text
Keywords: fourth-generation polyester-based lysine-modified dendrimer; physical encapsulation; ursolic acid (UA); Gram-positive MDR isolates; MICs; time-kill experiments; cytotoxicity on human keratinocytes fourth-generation polyester-based lysine-modified dendrimer; physical encapsulation; ursolic acid (UA); Gram-positive MDR isolates; MICs; time-kill experiments; cytotoxicity on human keratinocytes
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MDPI and ACS Style

Schito, A.M.; Caviglia, D.; Piatti, G.; Zorzoli, A.; Marimpietri, D.; Zuccari, G.; Schito, G.C.; Alfei, S. Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci. Pharmaceutics 2021, 13, 1976. https://doi.org/10.3390/pharmaceutics13111976

AMA Style

Schito AM, Caviglia D, Piatti G, Zorzoli A, Marimpietri D, Zuccari G, Schito GC, Alfei S. Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci. Pharmaceutics. 2021; 13(11):1976. https://doi.org/10.3390/pharmaceutics13111976

Chicago/Turabian Style

Schito, Anna M., Debora Caviglia, Gabriella Piatti, Alessia Zorzoli, Danilo Marimpietri, Guendalina Zuccari, Gian C. Schito, and Silvana Alfei. 2021. "Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci" Pharmaceutics 13, no. 11: 1976. https://doi.org/10.3390/pharmaceutics13111976

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