Evaluation of the efficiency of various methods to load fluoroquinolones into Escherichia coli outer membrane vesicles as a novel antibiotic delivery platform

The development of novel antibacterial agents that are effective against Gram-negative bacteria is limited primarily by transport issues. This class of bacteria maintains a complex cell envelope consisting of two membrane bilayers, preventing the passage of most antibiotics. These drugs must therefo...

Ausführliche Beschreibung

Bibliographische Detailangaben
Veröffentlicht in:Biochemical engineering journal. - 1998. - 210(2024) vom: 01. Okt.
1. Verfasser: Wu, Meishan (VerfasserIn)
Weitere Verfasser: Holgado, Lauryn, Harrower, Rachael M, Brown, Angela C
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Biochemical engineering journal
Schlagworte:Journal Article Gram-negative bacteria Outer membrane vesicles antibiotic resistance fluoroquinolones
LEADER 01000caa a22002652c 4500
001 NLM375795073
003 DE-627
005 20250306115627.0
007 cr uuu---uuuuu
008 240802s2024 xx |||||o 00| ||eng c
024 7 |a 10.1016/j.bej.2024.109418  |2 doi 
028 5 2 |a pubmed25n1251.xml 
035 |a (DE-627)NLM375795073 
035 |a (NLM)39092080 
035 |a (PII)109418 
040 |a DE-627  |b ger  |c DE-627  |e rakwb 
041 |a eng 
100 1 |a Wu, Meishan  |e verfasserin  |4 aut 
245 1 0 |a Evaluation of the efficiency of various methods to load fluoroquinolones into Escherichia coli outer membrane vesicles as a novel antibiotic delivery platform 
264 1 |c 2024 
336 |a Text  |b txt  |2 rdacontent 
337 |a ƒaComputermedien  |b c  |2 rdamedia 
338 |a ƒa Online-Ressource  |b cr  |2 rdacarrier 
500 |a Date Revised 06.08.2024 
500 |a published: Print-Electronic 
500 |a Citation Status PubMed-not-MEDLINE 
520 |a The development of novel antibacterial agents that are effective against Gram-negative bacteria is limited primarily by transport issues. This class of bacteria maintains a complex cell envelope consisting of two membrane bilayers, preventing the passage of most antibiotics. These drugs must therefore pass through protein channels called porins; however, many antibiotics are too large to pass through porins, and a common mechanism of acquired resistance is down-regulation of porins. To overcome this transport limitation, we have proposed the use of outer membrane vesicles (OMVs), released by Gram-negative bacteria, which deliver cargo to other bacterial cells in a porin-independent manner. In this work, we systematically studied the ability to load fluoroquinolones into purified Escherichia coli OMVs using in vivo and in vitro passive loading methods, and active loading methods such as electroporation and sonication. We observed limited loading of all of the antibiotics using passive loading techniques; sonication and electroporation significantly increased the loading, with electroporation at low voltages (200 and 400V) resulting in the greatest encapsulation efficiencies. We also demonstrated that imipenem, a carbapenem antibiotic, can be readily loaded into OMVs, and its administration via OMVs increases the effectiveness of the drug against E. coli. Our results demonstrate that small molecule antibiotics can be readily incorporated into OMVs to create novel delivery vehicles to improve antibiotic activity 
650 4 |a Journal Article 
650 4 |a Gram-negative bacteria 
650 4 |a Outer membrane vesicles 
650 4 |a antibiotic resistance 
650 4 |a fluoroquinolones 
700 1 |a Holgado, Lauryn  |e verfasserin  |4 aut 
700 1 |a Harrower, Rachael M  |e verfasserin  |4 aut 
700 1 |a Brown, Angela C  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Biochemical engineering journal  |d 1998  |g 210(2024) vom: 01. Okt.  |w (DE-627)NLM098270710  |x 1369-703X  |7 nnas 
773 1 8 |g volume:210  |g year:2024  |g day:01  |g month:10 
856 4 0 |u http://dx.doi.org/10.1016/j.bej.2024.109418  |3 Volltext 
912 |a GBV_USEFLAG_A 
912 |a SYSFLAG_A 
912 |a GBV_NLM 
912 |a GBV_ILN_350 
951 |a AR 
952 |d 210  |j 2024  |b 01  |c 10