Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/14598
Dual bioresponsive antibiotic and quorum sensing inhibitor combination nanoparticles for treatment of Pseudomonas aeruginosa biofilms in vitro and ex vivo
Identifiers
DOI: 10.1039/c9bm00773c
ISSN: 2047-4830
eISSN: 2047-4849
WOS ID: 000487753500010
Scopus EID: 2-s2.0-85072628126
PMID: 31355397
Embase PUI: L629427611
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2019-10-01Document type
research articleCitation
Singh Nishant, Romero M, Travanut A, Monteiro PF, Jordana-Lluch E, Hardie Kim R, et al. Dual bioresponsive antibiotic and quorum sensing inhibitor combination nanoparticles for treatment of Pseudomonas aeruginosa biofilms in vitro and ex vivo. Biomater Sci. 2019 Oct 01;7(10):4099-111.Abstract
Many debilitating infections result from persistent microbial biofilms that do not respond to conventional antibiotic regimens. A potential method to treat such chronic infections is to combine agents which interfere with bacterial biofilm development together with an antibiotic in a single formulation. Here, we explore the use of a new bioresponsive polymer formulation derived from specifically modified alginate nanoparticles (NPs) in order to deliver ciprofloxacin (CIP) in combination with the quorum sensing inhibitor (QSI) 3-amino-7-chloro-2-nonylquinazolin-4(3H)-one (ACNQ) to mature Pseudomonas aeruginosa biofilms. The alginate NPs were engineered to incorporate a pH-responsive linker between the polysaccharide backbone and the QSI, and to encapsulate CIP via charge-charge interactions of the positively-charged drug with the carboxyl residues of the alginate matrix. In this way, a dual-action release of antibiotic and QSI was designed for the low-pH regions of a biofilm, involving cleavage of the QSI-linker to the alginate matrix and reduced charge-charge interactions between CIP and the polysaccharide as the alginate carboxyl side-chains protonated. When tested in a biofilm model the concomitant release of CIP + QSI from the pH-responsive nanoparticles significantly reduced the viability of the biofilm compared with CIP treatment alone. In addition, the alginate NPs were shown to penetrate deeply into P. aeruginosa biofilms, which we attribute in part to the charges of the NPs and the release of the QSI agent. Finally, we tested the formulation in both a 2D keratinocyte and a 3D ex vivo skin infection model. The dual-action bio-responsive QSI and CIP release nanoparticles effectively cleared the infection in the latter, suggesting considerable promise for combination therapeutics which prevent biofilm formation as well as effectively killing mature P. aeruginosa biofilms.
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https://dx.doi.org/10.1039/c9bm00773cMeSH
BiofilmsNanoparticles
Microbial Sensitivity Tests
Animals
Quorum Sensing
Humans
Cell Line
Ciprofloxacin
Hydrogen-Ion Concentration
Pseudomonas aeruginosa
Swine
Pseudomonas Infections
DeCS
CiprofloxacinaConcentración de Iones de Hidrógeno
Animales
Percepción de Quorum
Pruebas de Sensibilidad Microbiana
Porcinos
Humanos
Nanopartículas
Infecciones por Pseudomonas
Pseudomonas aeruginosa
Línea Celular
Biopelículas