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Targeting Intracellular Bacteria with Dual Drug-loaded Lactoferrin Nanoparticles.
Andima, Moses; Boese, Annette; Paul, Pascal; Koch, Marcus; Loretz, Brigitta; Lehr, Claus-Micheal.
Afiliación
  • Andima M; Department of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Campus E8.1, Saarbrücken 66123, Germany.
  • Boese A; Department of Chemistry, Faculty of Science and Education, Busitema University, P.O Box 236, Tororo 21435, Uganda.
  • Paul P; Department of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Campus E8.1, Saarbrücken 66123, Germany.
  • Koch M; Department of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Campus E8.1, Saarbrücken 66123, Germany.
  • Loretz B; INM-Leibniz Institute for New Materials, Campus D2 2, Saarbrücken 66123, Germany.
  • Lehr CM; Department of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Campus E8.1, Saarbrücken 66123, Germany.
ACS Infect Dis ; 10(5): 1696-1710, 2024 05 10.
Article en En | MEDLINE | ID: mdl-38577780
ABSTRACT
Treatment of microbial infections is becoming daunting because of widespread antimicrobial resistance. The treatment challenge is further exacerbated by the fact that certain infectious bacteria invade and localize within host cells, protecting the bacteria from antimicrobial treatments and the host's immune response. To survive in the intracellular niche, such bacteria deploy surface receptors similar to host cell receptors to sequester iron, an essential nutrient for their virulence, from host iron-binding proteins, in particular lactoferrin and transferrin. In this context, we aimed to target lactoferrin receptors expressed by macrophages and bacteria; as such, we prepared and characterized lactoferrin nanoparticles (Lf-NPs) loaded with a dual drug combination of antimicrobial natural alkaloids, berberine or sanguinarine, with vancomycin or imipenem. We observed increased uptake of drug-loaded Lf-NPs by differentiated THP-1 cells with up to 90% proportion of fluorescent cells, which decreased to about 60% in the presence of free lactoferrin, demonstrating the targeting ability of Lf-NPs. The encapsulated antibiotic drug cocktail efficiently cleared intracellular Staphylococcus aureus (Newman strain) compared to the free drug combinations. However, the encapsulated drugs and the free drugs alike exhibited a bacteriostatic effect against the hard-to-treat Mycobacterium abscessus (smooth variant). In conclusion, the results of this study demonstrate the potential of lactoferrin nanoparticles for the targeted delivery of antibiotic drug cocktails for the treatment of intracellular bacteria.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus / Nanopartículas / Lactoferrina / Antibacterianos Límite: Humans Idioma: En Revista: ACS Infect Dis Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus / Nanopartículas / Lactoferrina / Antibacterianos Límite: Humans Idioma: En Revista: ACS Infect Dis Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos