TY  - JOUR
U1  - Wissenschaftlicher Artikel
A1  - Drost, Menka
A1  - Diamanti, Eleonora
A1  - Fuhrmann, Kathrin
A1  - Goes, Adriely
A1  - Shams, Atanaz
A1  - Haupenthal, Jörg
A1  - Koch, Marcus
A1  - Hirsch, Anna Katharina H.
A1  - Fuhrmann, Gregor
T1  - Bacteriomimetic Liposomes Improve Antibiotic Activity of a Novel Energy-Coupling Factor Transporter Inhibitor
JF  - Pharmaceutics
N2  - 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.
KW  - liposomes
KW  - nanoantibiotics
KW  - energy-coupling factors (ECF) transporters
KW  - bacteriomimetic
KW  - bacillus subtilis
Y1  - 2022
UN  - https://nbn-resolving.org/urn:nbn:de:bsz:291:415-117
SN  - 1999-4923
SS  - 1999-4923
U6  - https://doi.org/10.3390/pharmaceutics14010004
DO  - https://doi.org/10.3390/pharmaceutics14010004
VL  - 14
IS  - 4
SP  - 1
EP  - 19
ER  -