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International Journal of PharmaceuticsVolume 519, Issue 1-2, 15 March 2017, Pages 128-137

Docosahexaenoic acid loaded lipid nanoparticles with bactericidal activity against Helicobacter pylori(Article)

  • Seabra, C.L.,
  • Nunes, C.,
  • Gomez-Lazaro, M.,
  • Correia, M.,
  • Machado, J.C.,
  • Gonçalves, I.C.,
  • Reis, C.A.,
  • Reis, S.,
  • Martins, M.C.L.
  • View Correspondence (jump link)
  • ai3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal, 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
  • fEscola da Saúde, Universidade do Algarve, Portugal
  • gFaculdade de Medicina, Universidade do Porto, Portugal

Abstract

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid present in fish oil, has been described as a promising molecule to the treatment of Helicobacter pylori gastric infection. However, due to its highly unsaturated structure, DHA can be easily oxidized loosing part of its bioactivity. This work aims the nanoencapsulation of DHA to improve its bactericidal efficacy against H. pylori. DHA was loaded into nanostructured lipid carriers (NLC) produced by hot homogenization and ultrasonication using a blend of lipids (Precirol ATO5®, Miglyol-812®) and a surfactant (Tween 60®). Homogeneous NLC with 302 ± 14 nm diameter, −28 ± 3 mV surface charge (dynamic and electrophoretic light scattering) and containing 66 ± 7% DHA (UV/VIS spectroscopy) were successfully produced. Bacterial growth curves, performed over 24 h in the presence of different DHA concentrations (free or loaded into NLC), demonstrated that nanoencapsulation enhanced DHA bactericidal effect, since DHA-loaded NLC were able to inhibit H. pylori growth in a much lower concentrations (25 μM) than free DHA (>100 μM). Bioimaging studies, using scanning and transmission electron microscopy and also imaging flow cytometry, demonstrated that DHA-loaded NLC interact with H. pylori membrane, increasing their periplasmic space and disrupting membrane and allowing the leakage of cytoplasmic content. Furthermore, the developed nanoparticles are not cytotoxic to human gastric adenocarcinoma cells at bactericidal concentrations. DHA-loaded NLC should, therefore, be envisaged as an alternative to the current treatments for H. pylori infection. © 2017 Elsevier B.V.

Author keywords

Docosahexaenoic acid (DHA)Helicobacter pyloriNanostructured lipid carriers (NLC)Polyunsaturated fatty acid (PUFA)

Indexed keywords

EMTREE drug terms:docosahexaenoic acidlipidmiglyolnanoparticlesurfactantantiinfective agentdocosahexaenoic aciddrug carrierfish oillipidnanomaterialnanoparticlepolysorbate
EMTREE medical terms:antibacterial activityArticlebacterial growthbactericidal activitybiocompatibilitycolony forming unitHelicobacter pylorihumanhuman cellmolecular weightMTT assaynanoencapsulationperiplasmphoton correlation spectroscopypriority journalscanning electron microscopytransmission electron microscopyultraviolet spectrophotometrychemistrydrug effectsHelicobacter InfectionsHelicobacter pylorimicrobiologyparticle sizestomachtumor cell line
MeSH:Anti-Bacterial AgentsCell Line, TumorDocosahexaenoic AcidsDrug CarriersFish OilsHelicobacter InfectionsHelicobacter pyloriHumansLipidsNanoparticlesNanostructuresParticle SizePolysorbatesStomachSurface-Active Agents

Chemicals and CAS Registry Numbers:

docosahexaenoic acid, 25167-62-8, 32839-18-2; lipid, 66455-18-3; miglyol, 37332-31-3, 77466-09-2, 77944-80-0, 97708-73-1; fish oil, 8016-13-5; polysorbate, 9005-63-4;

Anti-Bacterial Agents; Docosahexaenoic Acids; Drug Carriers; Fish Oils; Lipids; Polysorbates; Surface-Active Agents

  • ISSN: 03785173
  • CODEN: IJPHD
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.ijpharm.2017.01.014
  • PubMed ID: 28088639
  • Document Type: Article
  • Publisher: Elsevier B.V.

  Martins, M.C.L.; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal;
© Copyright 2018 Elsevier B.V., All rights reserved.

Cited by 9 documents

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Intracellular staphylococcus aureus elicits the production of host very long-chain saturated fatty acids with antimicrobial activity
(2019) Metabolites
Lopes-De-Campos, D. , Pinto, R.M. , Costa Lima, S.A.
Delivering amoxicillin at the infection site-a rational design through lipid nanoparticles
(2019) International Journal of Nanomedicine
View details of all 9 citations
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