Oral administration of quercetin-loaded mare's milk derived exosomes
reversed age induced organ damage in rats
Abstract
Exosomes are cell derived and membrane-surrounded particles that deliver
bioactive molecules to various cells. Their small size, low
immunogenicity, extended blood circulation, and involvement in cellular
communication make them a potentially effective drug carrier. Exosomes
found in different biological fluids including mare’s milk, a
traditional drink in central Asia. Therefore, the aim of this study is
to compare exosomes isolation methodology and determine the stability of
mare’s milk-derived exosomes as potential therapeutic carrier. Three
extraction methods namely, immunoprecipitation, size exclusion
chromatography, and total exosome isolation were compared in terms of
exosome characteristics, purity, and content. The isolated exosomes then
loaded with quercetin and their ability of increasing its
bioavailability were tested in vitro and in vivo. Out of the three
tested methods, total exosome isolation appeared to be the most
efficient method that produced good quality exosomes, which were then
loaded with quercetin and compared to free quercetin and exosomes only.
Interestingly, exosomes loaded with 80µM quercetin significantly
restored β-galactosidase activity and cellular viability in doxorubicin
treated cells more than negative control and exosomes only, with a
potency similar to that of 160µM free quercetin. Interestingly, aged
model animals treated with exosomes loaded with quercetin showed
significantly less frequent patterns of acute and subacute damage in the
myocardium, kidneys, and liver compared to the untreated control group
of aged models. The current study is a proof-of-concept that shows
mare’s milk-derived exosomes are able to be absorbed by cells and animal
tissues, which support their potential use as drug carrier.