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 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