Bioinspired liposomes for oral delivery of colistin to combat intracellular infections by Salmonella enterica

Sara Menina, Janina Eisenbeis, Mohamed Ashraf M. Kamal, Marcus Koch, Markus Bischoff, Sarah Gordon, Brigitta Loretz, Claus Michael Lehr

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Bacterial invasion into eukaryotic cells and the establishment of intracellular infection has proven to be an effective means of resisting antibiotic action, as anti-infective agents commonly exhibit a poor permeability across the host cell membrane. Encapsulation of anti-infectives into nanoscaled delivery systems, such as liposomes, is shown to result in an enhancement of intracellular delivery. The aim of the current work is, therefore, to formulate colistin, a poorly permeable anti-infective, into liposomes suitable for oral delivery, and to functionalize these carriers with a bacteria-derived invasive moiety to enhance their intracellular delivery. Different combinations of phospholipids and cholesterol are explored to optimize liposomal drug encapsulation and stability in biorelevant media. These liposomes are then surface-functionalized with extracellular adherence protein (Eap), derived from Staphylococcus aureus. Treatment of HEp-2 and Caco-2 cells infected with Salmonella enterica using colistin-containing, Eap-functionalized liposomes resulted in a significant reduction of intracellular bacteria, in comparison to treatment with nonfunctionalized liposomes as well as colistin alone. This indicates that such bio-invasive carriers are able to facilitate intracellular delivery of colistin, as necessary for intracellular anti-infective activity. The developed Eap-functionalized liposomes, therefore, present a promising strategy for improving the therapy of intracellular infections.

Original languageEnglish
Article number1900564
JournalAdvanced Healthcare Materials
Volume8
Issue number17
Early online date22 Jul 2019
DOIs
Publication statusPublished - 5 Sep 2019

Keywords

  • bacterial invasion
  • bacteriomimetic nanocarriers
  • Eap
  • extracellular adherence proteins
  • simulated intestinal fluids
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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