Aptamer-Guided Antibiotic-Loaded Exosomes for Improved Treatment of Bacterial Wound Infections

One mechanism of antibiotic resistance is bacterial expulsion of antibiotics via efflux pumps.Ā However, if one could deliver more concentrated antibiotic intracellularly in both human and bacterial cells in wounds, one might overcome this antibacterial efflux mechanism. ĀThus, Nanohmics Inc. proposes to develop various antibiotics packaged inside exosomes of human or lower cost yeast origin in culture.Ā After the antibiotic-loaded exosomes are purified using spin columns, they will be labeled by attaching DNA aptamers specific for antibiotic-resistant ESKAPE pathogens such as the common KDO core antigen of LPS using bifunctional linkers and tested in vitro in Phase I by colony counts versus antibiotic-loaded exosomes with and without KDO aptamers and antibiotics alone (not exosome-encased) at the same concentrations. ĀThe aptamer-exosome-encased antibiotic product will also be lyophilized and rehydrated in Phase I to test the stability of the product in in vitro bacterial killing tests against antibiotic-resistant ESKAPE pathogens (e.g., KPC). In Phase II, testing will progress to in vivo animal models followed by IND filing with the FDA.Ā Texas State University will verify and characterize the presence of exosomes, their size distribution and their antibiotic contents using electron microscopy and HPLC before and after lyophilization/rehydration of the antibiotic-loaded aptamer-exosome products.