TY - JOUR
T1 - Lipid nanoparticles to counteract gastric infection without affecting gut microbiota
AU - Seabra, Catarina Leal
AU - Nunes, Cláudia
AU - Brás, Manuela
AU - Gomez-Lazaro, Maria
AU - Reis, Celso A.
AU - Gonçalves, Inês C.
AU - Reis, Salette
AU - Martins, M. Cristina L.
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
KW - Bactericidal
KW - H. pylori membrane disruption
KW - Microbiota
KW - Nanostructured lipid carriers
KW - NLC
UR - http://www.scopus.com/inward/record.url?scp=85044023662&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2018.02.030
DO - 10.1016/j.ejpb.2018.02.030
M3 - Article
C2 - 29524597
AN - SCOPUS:85044023662
SN - 0939-6411
VL - 127
SP - 378
EP - 386
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -