%0 Journal Article
%T Oral Administration Properties Evaluation of Three Milk-Derived Extracellular Vesicles Based on Ultracentrifugation Extraction Methods.
%A Xia B
%A Hu R
%A Chen J
%A Shan S
%A Xu F
%A Zhang G
%A Zhou Z
%A Fan Y
%A Hu Z
%A Liang XJ
%J Adv Healthc Mater
%V 0
%N 0
%D 2024 May 20
%M 38767497
%F 11.092
%R 10.1002/adhm.202401370
%X Milk-derived extracellular vesicles (M-EVs) are low-cost, can be prepared in large quantities, and can cross the gastrointestinal barrier for oral administration. However, the composition of milk is complex, and M-EVs obtained by different extraction methods may affect their oral delivery. Based on this, a new method for extracting M-EVs based on cryogenic freezing treatment (Cryo-M-EVs) is proposed and compared with the previously reported acetic acid treatment (Acid-M-EVs) method and the conventional ultracentrifugation method (Ulltr-M-EVs). The new method simplifies the pretreatment step and achieves 25-fold and twofold higher yields than Acid-M-EVs and Ulltr-M-EVs. And it is interesting to note that Cryo-M-EVs and Acid-M-EVs have higher cellular uptake efficiency, and Cryo-M-EVs present the best transepithelial transport effect. After oral administration of the three M-EVs extracted by three methods in mice, Cryo-M-EVs effectively successfully cross the gastrointestinal barrier and achieve hepatic accumulation, whereas Acid-M-EVs and Ultr-M-EVs mostly reside in the intestine. The M-EVs obtained by the three extraction methods show a favorable safety profile at the cellular as well as animal level. Therefore, when M-EVs obtained by different extraction methods are used for oral drug delivery, their accumulation properties at different sites can be utilized to better deal with different diseases.