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Bacteriomimetic Liposomes Improve Antibiotic Activity of a Novel Energy-Coupling Factor Transporter Inhibitor

  • Liposomes have been studied for decades as nanoparticulate drug delivery systems for cytostatics, and more recently, for antibiotics. Such nanoantibiotics show improved antibacterial efficacy compared to the free drug and can be effective despite bacterial recalcitrance. In this work, we present a loading method of bacteriomimetic liposomes for a novel, hydrophobic compound (HIPS5031) inhibiting energy-coupling factor transporters (ECF transporters), an underexplored antimicrobial target. The liposomes were composed of DOPG (18:1 (Δ9-cis) phosphatidylglycerol) and CL (cardiolipin), resembling the cell membrane of Gram-positive Staphylococcus aureus and Streptococcus pneumoniae, and enriched with cholesterol (Chol). The size and polydispersity of the DOPG/CL/± Chol liposomes remained stable over 8 weeks when stored at 4 °C. Loading of the ECF transporter inhibitor was achieved by thin film hydration and led to a high encapsulation efficiency of 33.19% ± 9.5% into the DOPG/CL/Chol liposomes compared to the phosphatidylcholine liposomes (DMPC/DPPC). Bacterial growth inhibition assays on the model organism Bacillus subtilis revealed liposomal HIPS5031 as superior to the free drug, showing a 3.5-fold reduction in CFU/mL at a concentration of 9.64 µM. Liposomal HIPS5031 was also shown to reduce B. subtilis biofilm. Our findings present an explorative basis for bacteriomimetic liposomes as a strategy against drug-resistant pathogens by surpassing the drug-formulation barriers of innovative, yet unfavorably hydrophobic, antibiotics.

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Metadaten
Document Type:Article
Author:Menka DrostORCiD, Eleonora DiamantiORCiD, Kathrin Fuhrmann, Adriely GoesORCiD, Atanaz Shams, Jörg HaupenthalORCiD, Marcus Koch, Anna Katharina H. HirschORCiD, Gregor FuhrmannORCiD
URN:urn:nbn:de:bsz:291:415-117
DOI:https://doi.org/10.3390/pharmaceutics14010004
ISSN:1999-4923
Parent Title (English):Pharmaceutics
Volume:14
Issue:4
First Page:1
Last Page:19
Language:English
Date of Publication (online):2021/12/21
Year of first Publication:2022
Release Date:2022/05/09
Tag:bacillus subtilis; bacteriomimetic; energy-coupling factors (ECF) transporters; liposomes; nanoantibiotics
Impact:06.321 (2020)
Impact:06.525 (2021)
Funding Information:Federal Ministry of Education and Research (13XP5029A)
Groups:Physikalische Analytik
Researchfields:Servicebereich
DDC classes:600 Technik, Medizin, angewandte Wissenschaften / 610 Medizin, Gesundheit
Open Access:Open Access
Signature:INM 2022/015
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International