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European Journal of Pharmaceutics and BiopharmaceuticsVolume 127, June 2018, Pages 378-386

Lipid nanoparticles to counteract gastric infection without affecting gut microbiota(Article)

  • ai3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
  • bINEB – Instituto de Engenharia Biomédica, Universidade do Porto, Portugal
  • cIPATIMUP – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Portugal
  • dICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal
  • eUCIBIO, REQUIMTE, Laboratório de Química Aplicada, Faculdade de Farmácia, Universidade do Porto, Portugal
  • fFaculdade de Medicina, Universidade do Porto, Portugal

Abstract

Helicobacter pylori infection is one of the major risk factors for gastric cancer development. Available antibiotic-based treatments not only fail in around 20% of patients but also have a severe negative impact on the gut microbiota. Recently, we demonstrated that nanostructured lipid carriers (NLC), even without any drug loaded, are bactericidal against H. pylori at low concentrations. This work aims to clarify NLC mode of action and to evaluate if their bactericidal effect is specific to H. pylori without affecting bacteria from microbiota. NLC were produced by hot homogenization followed by ultrasonication method, using Precirol®ATO5 and Miglyol®812 as lipids and Tween®60 as a surfactant. NLC were able to eradicate H. pylori without affecting the other tested bacteria (Lactobacillus, E. coli, S. epidermidis and S. aureus). Bioimaging assays demonstrated that NLC rapidly bind to and cross the H. pylori bacterial membrane, destabilizing and disrupting it, which leads to leakage of the cytoplasmic contents and consequent bacterial death. In an era where efficient alternatives to antibiotics are urgent, NLC are an interesting route to be explored in the quest for new antibiotic-free therapies to fight H. pylori infection. © 2018 Elsevier B.V.

Author keywords

BactericidalH. pylori membrane disruptionMicrobiotaNanostructured lipid carriersNLC

Indexed keywords

EMTREE drug terms:glycerol palmitostearatemiglyolnanocarriernanostructured lipid carrierpolysorbate 60solid lipid nanoparticleunclassified drugantiinfective agentdrug carrierlipidnanomaterialnanoparticlesurfactant
EMTREE medical terms:Articlebacterial clearancebacterial membranebactericidal activitycontrolled studycytoplasmEscherichia coliHelicobacter infectionintestine floraLactobacillusminimum inhibitory concentrationnonhumanStaphylococcus aureusStaphylococcus epidermidissurface chargezeta potentialbacteriumchemistrydrug effectHelicobacter infectionHelicobacter pylorihumanintestine floramicrofloraparticle size
MeSH:Anti-Bacterial AgentsBacteriaDrug CarriersGastrointestinal MicrobiomeHelicobacter InfectionsHelicobacter pyloriHumansLipidsMicrobiotaNanoparticlesNanostructuresParticle SizeSurface-Active Agents

Chemicals and CAS Registry Numbers:

glycerol palmitostearate, 29593-61-1; miglyol, 37332-31-3, 77466-09-2, 77944-80-0, 97708-73-1; polysorbate 60, 9005-67-8; lipid, 66455-18-3;

Anti-Bacterial Agents; Drug Carriers; Lipids; Surface-Active Agents

Funding details

Funding sponsor Funding number Acronym
Fundação para a Ciência e a Tecnologia
See opportunities		SFRH/BD/89001/ 2012
POCI
PTDC/CTM-BIO/ 4043/2014,NORTE-01-0145-FEDER-000012,POCI-01-0145-FEDER-007274

  • 1

    This work was financed by FEDER funds through the COMPETE 2020 (POCI), Portugal 2020. FCT/MCTES through the projects: POCI-01-0145-FEDER-007274; PYLORIBINDERS (PTDC/CTM-BIO/ 4043/2014); NORTE-01-0145-FEDER-000012 and FCT grant SFRH/BD/89001/ 2012. DLS, ELS, and AFM were performed at BN-Biointerfaces and Nanotechnology unit facility; imaging flow cytometry at b.IMAGE-Bioimaging Center for Biomaterials and Regenerative Therapies, TEM at HEMS – Histology and Electron Microscopy Service Unit facility. All of these unit facilities are located at i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto (www.i3s.up.pt/research/scientific-platforms). SEM studies were performed at the CEMUP- Centro de Materiais da Universidade do Porto (http:/www.cemup.up.pt). The authors thank Prof. Manuela Pintado (Universidade Católica do Porto, Portugal) for providing the Lactobacillus casei -01 strain; and Prof. Thomas Boren (Umeã University, Sweden) for providing the H. pylori J99 strain.

  • ISSN: 09396411
  • CODEN: EJPBE
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.ejpb.2018.02.030
  • PubMed ID: 29524597
  • Document Type: Article
  • Publisher: Elsevier B.V.

  Martins, M.C.L.; i3S – Instituto de Investigação e Inovação em Saúde, INEB-Instituto de Engenharia Biomédica, Rua Alfredo Allen, 208, Porto, Portugal;
© Copyright 2018 Elsevier B.V., All rights reserved.

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Häfner, S.J.
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(2018) Microbes and Infection
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