Coupling quaternary ammonium surfactants to the surface of liposomes improves both antibacterial efficacy and host cell biocompatibility

Carlos V Montefusco-Pereira; Beatrice Formicola; Adriely Goes; Francesca Re; Claudia A Marrano; Francesco Mantegazza; Cristiane Carvalho-Wodarz; Gregor Fuhrmann; Enrico Caneva; Francesco Nicotra; Claus-Michael Lehr; Laura Russo

doi:10.1016/j.ejpb.2020.01.013

Coupling quaternary ammonium surfactants to the surface of liposomes improves both antibacterial efficacy and host cell biocompatibility

Eur J Pharm Biopharm. 2020 Apr:149:12-20. doi: 10.1016/j.ejpb.2020.01.013. Epub 2020 Jan 31.

Affiliations

¹ Department of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, Saarbrücken 66123, Germany; Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany. Electronic address: carlos.montefusco@helmholtz-hips.de.
² School of Medicine and Surgery, Nanomedicine Center NANOMIB, University of Milano-Bicocca (UNIMIB), Via Raoul Follereau 3, 20854 Vedano al Lambro (MB), Italy. Electronic address: b.formicola@campus.unimib.it.
³ Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany; Biogenic Nanotherapeutics Group (BION), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, Saarbrücken 66123, Germany. Electronic address: adriely.goes@helmholtz-hips.de.
⁴ School of Medicine and Surgery, Nanomedicine Center NANOMIB, University of Milano-Bicocca (UNIMIB), Via Raoul Follereau 3, 20854 Vedano al Lambro (MB), Italy. Electronic address: francesca.re1@unimib.it.
⁵ School of Medicine and Surgery, Nanomedicine Center NANOMIB, University of Milano-Bicocca (UNIMIB), Via Raoul Follereau 3, 20854 Vedano al Lambro (MB), Italy. Electronic address: claudia.marrano@unimib.it.
⁶ School of Medicine and Surgery, Nanomedicine Center NANOMIB, University of Milano-Bicocca (UNIMIB), Via Raoul Follereau 3, 20854 Vedano al Lambro (MB), Italy. Electronic address: francesco.mantegazza@unimib.it.
⁷ Department of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, Saarbrücken 66123, Germany. Electronic address: cristiane.carvalho@helmholtz-hips.de.
⁸ Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany; Biogenic Nanotherapeutics Group (BION), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, Saarbrücken 66123, Germany. Electronic address: gregor.fuhrmann@helmholtz-hips.de.
⁹ UNITECH COSPECT: Comprehensive Substances characterization via advanced sPECTtrometry, 20133 Milan, Italy. Electronic address: enrico.caneva@unimi.it.
¹⁰ Bio Organic Chemistry Laboratory, Department of Biotechnology and Biosciences, University of Milan - Bicocca (UNIMIB), Piazza della Scienza 2, 20126 Milan, Italy. Electronic address: francesco.nicotra@unimib.it.
¹¹ Department of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, Saarbrücken 66123, Germany; Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany. Electronic address: claus-michael.lehr@helmholtz-hips.de.
¹² Bio Organic Chemistry Laboratory, Department of Biotechnology and Biosciences, University of Milan - Bicocca (UNIMIB), Piazza della Scienza 2, 20126 Milan, Italy. Electronic address: laura.russo@unimib.it.

PMID: 32007589
DOI: 10.1016/j.ejpb.2020.01.013

Abstract

By functionalizing the surface of PEG-liposomes with linkers bearing quaternary ammonium compounds (QACs), we generated novel bacteria disruptors with anti-adhesive properties and reduced cytotoxicity compared to free QACs. Furthermore, QAC-functionalized liposomes are a promising platform for future drug encapsulation. The QAC (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide (MTAB) was attached to maleimide-functionalized liposomes (DSPE-PEG) via thiol linker. The MTAB-functionalized liposomes were physicochemically characterized and their biological activity, in terms of anti-adherence activity and biofilm prevention in Escherichia coli were assessed. The results showed that MTAB-functionalized liposomes inhibit bacterial adherence and biofilm formation while reducing MTAB toxicity.

Keywords: Anti-adherence nanoparticles; Bacterial biofilm; Liposomes; Quarternary ammonium functionalization.

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Biofilms / drug effects*
Escherichia coli / drug effects*
Liposomes
Maleimides / chemistry
Nanoparticles
Phosphatidylethanolamines / chemistry
Polyethylene Glycols / chemistry
Quaternary Ammonium Compounds / chemistry
Quaternary Ammonium Compounds / pharmacology*
Sulfhydryl Compounds / chemistry
Sulfhydryl Compounds / pharmacology*
Surface-Active Agents / chemistry
Surface-Active Agents / pharmacology

Substances

(16-mercaptohexadecyl)trimethylammonium bromide
Anti-Bacterial Agents
Liposomes
Maleimides
Phosphatidylethanolamines
Quaternary Ammonium Compounds
Sulfhydryl Compounds
Surface-Active Agents
polyethylene glycol-distearoylphosphatidylethanolamine
maleimide
Polyethylene Glycols