Oral Administration Properties Evaluation of Three Milk-Derived Extracellular Vesicles Based on Ultracentrifugation Extraction Methods.

Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101581613 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2192-2659 (Electronic) Linking ISSN: 21922640 NLM ISO Abbreviation: Adv Healthc Mater Subsets: MEDLINE

Original Publication: Weinheim : Wiley-VCH, 2012-

Extracellular Vesicles*/chemistry ; Extracellular Vesicles*/metabolism ; Milk*/chemistry ; Ultracentrifugation*/methods; Animals ; Administration, Oral ; Mice ; Humans ; Caco-2 Cells

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.
(© 2024 Wiley‐VCH GmbH.)

R. Kalluri, V. S. LeBleu, Science 2020, 367, eaau6977.
J. Skog, T. Würdinger, S. van Rijn, D. H. Meijer, L. Gainche, M. Sena‐Esteves, W. T. Curry Jr, B. S. Carter, A. M. Krichevsky, X. O. Breakefield, Nat. Cell Biol. 2008, 10, 1470.
J. Chen, G. Zhang, Y. Wan, B. Xia, Q. Ni, S. Shan, Z. Hu, X. J. Liang, J Control Release 2023, 364, 508.
X. Cai, F. Janku, Q. Zhan, J. B. Fan, Trends Genet. 2015, 31, 564.
A. Hoshino, B. Costa‐Silva, T. L. Shen, G. Rodrigues, A. Hashimoto, M. Tesic Mark, H. Molina, S. Kohsaka, A. Di Giannatale, S. Ceder, S. Singh, C. Williams, N. Solop, K. Uryu, L. Pharmer, T. King, L. Bojmar, A. E. Davies, Y. Ararso, T. Zhang, H. Zhang, J. Hernandez, J. M. Weiss, V. D. Dumont‐Cole, K. Kramer, L. H. Wexler, A. Narendran, G. K. Schwartz, J. H. Healey, et al., Nature 2015, 527, 329.
J. Jiang, J. Mei, Y. Ma, S. Jiang, J. Zhang, S. Yi, C. Feng, Y. Liu, Y. Liu, Exploration 2022, 2, 20210144.
M. Cully, Nat Rev Drug Discov 2021, 20, 6.
V. P. Chavda, G. Luo, R. Bezbaruah, T. Kalita, A. Sarma, G. Deka, Y. Duo, B. K. Das, Y. Shah, H. Postwala, Exploration 2024, 20230139.
S. Shan, J. Chen, Y. Sun, Y. Wang, B. Xia, H. Tan, C. Pan, G. Gu, J. Zhong, G. Qing, Y. Zhang, J. Wang, Y. Wang, Y. Wang, P. Zuo, C. Xu, F. Li, W. Guo, L. Xu, M. Chen, Y. Fan, L. Zhang, X. J. Liang, Adv. Sci. 2022, 9, 2200353.
J. Chen, Y. Xu, X. Wang, D. Liu, F. Yang, X. Zhu, Y. Lu, W. Xing, Lab Chip 2019, 19, 432.
Y. L. Zhang, Y. L. Wang, K. Yan, H. Li, X. Zhang, J. M. Essola, C. Ding, K. Chang, G. Qing, F. Zhang, Y. Tan, T. Peng, X. Wang, M. Jiang, X. J. Liang, Q. Hua, Adv. Sci. 2023, 2306140.
T. Wolf, S. R. Baier, J. Zempleni, J. Nutr. 2015, 145, 2201.
M. Samuel, P. Fonseka, R. Sanwlani, L. Gangoda, S. H. Chee, S. Keerthikumar, A. Spurling, S. V. Chitti, D. Zanker, C. S. Ang, I. Atukorala, T. Kang, S. Shahi, A. L. Marzan, C. Nedeva, C. Vennin, M. C. Lucas, L. Cheng, D. Herrmann, M. Pathan, D. Chisanga, S. C. Warren, K. Zhao, N. Abraham, S. Anand, S. Boukouris, C. G. Adda, L. Jiang, T. M. Shekhar, N. Baschuk, et al., Nat. Commun. 2021, 12, 3950.
J. Zhong, B. Xia, S. Shan, A. Zheng, S. Zhang, J. Chen, X. J. Liang, Biomaterials 2021, 277, 121126.
J. L. Betker, B. M. Angle, M. W. Graner, T. J. Anchordoquy, J. Pharm. Sci. 2019, 108, 1496.
O. J. Arntz, B. C. Pieters, M. C. Oliveira, M. G. Broeren, M. B. Bennink, M. de Vries, P. L. van Lent, M. I. Koenders, W. B. van den Berg, P. M. van der Kraan, F. A. J. van de Loo, Mol. Nutr. Food Res. 2015, 59, 1701.
G. Han, H. Kim, H. Jang, E. S. Kim, S. H. Kim, Y. Yang, Bioact Mater 2024, 34, 138.
A. K. Agrawal, F. Aqil, J. Jeyabalan, W. A. Spencer, J. Beck, B. W. Gachuki, S. S. Alhakeem, K. Oben, R. Munagala, S. Bondada, R. C. Gupta, Nanomedicine 2017, 13, 1627.
L. Tong, H. Hao, Z. Zhang, Y. Lv, X. Liang, Q. Liu, T. Liu, P. Gong, L. Zhang, F. Cao, G. Pastorin, C. N. Lee, X. Chen, J.‐W. Wang, H. Yi, Theranostics 2021, 11, 8570.
C. Théry, S. Amigorena, G. Raposo, A. Clayton, Curr Protoc Cell Biol. 2006, http://doi.org/10.1002/0471143030.cb0322s30.
H. Bao, Y. Tian, H. Wang, T. Ye, S. Wang, J. Zhao, Y. Qiu, J. Li, C. Pan, G. Ma, W. Wei, Y. Tao, Nat. Biomed. Eng. 2023.
P. Li, M. Kaslan, S. H. Lee, J. Yao, Z. Gao, Theranostics 2017, 7, 789.
M. Somiya, Y. Yoshioka, T. Ochiya, J Extracell Vesicles 2018, 7, 1440132.
D. Li, L. Gong, H. Lin, S. Yao, Y. Yin, Z. Zhou, J. Shi, Z. Wu, Z. Huang, Cells 2022, 11, 3065.
J. Qu, L. Zhang, L. Yin, J. Liu, Z. Sun, P. Zhou, Food Chem. 2021, 352, 129436.
K. H. Barbas, K. O'Brien, P. W. Forbes, M. B. Belfort, J. A. Connor, R. R. Thiagarajan, S. Y. Huh, JPEN, J. Parenter. Enteral Nutr. 2020, 44, 895.
Ö. Kaya, N. Çınar, Midwifery 2023, 118, 103519.
Z. Yu, C. Qiao, X. Zhang, L. Yan, L. Li, Y. Liu, J. Dairy Sci. 2021, 104, 4108.
L. Tong, S. Zhang, Q. Liu, C. Huang, H. Hao, M. S. Tan, X. Yu, C. K. L. Lou, R. Huang, Z. Zhang, T. Liu, P. Gong, C. H. Ng, M. Muthiah, G. Pastorin, M. G. Wacker, X. Chen, G. Storm, C. N. Lee, L. Zhang, H. Yi, J.‐W. Wang, Sci. Adv. 2023, 9, eade5041.
F. Zhang, B. Xia, J. Sun, Y. Wang, J. Wang, F. Xu, J. Chen, M. Lu, X. Yao, P. Timashev, Y. Zhang, M. Chen, J. Che, F. Li, X. J. Liang, Research 2022, 2022, 9808429.
H. Kim, D. E. Kim, G. Han, N. R. Lim, E. H. Kim, Y. Jang, H. Cho, H. Jang, K. H. Kim, S. H. Kim, Y. Yang, Adv. Healthcare Mater. 2022, 11, 2102027.
Y. Chen, L. Gong, Y. Cao, Z. Liu, Y. Wang, H. Cheng, Y. Feng, S. Yao, Y. Yin, Z. Wu, Z. Huang, J Control Release 2024, 366, 395.
L. Tong, H. Hao, X. Zhang, Z. Zhang, Y. Lv, L. Zhang, H. Yi, Mol. Nutr. Food Res. 2020, 64, e1901251.
J. J. Zou, G. Wei, C. Xiong, Y. Yu, S. Li, L. Hu, S. Ma, J. Tian, Sci. Adv. 2022, 8, eabm4677.
E. Tóth, L. Turiák, T. Visnovitz, C. Cserép, A. Mázló, B. W. Sódar, A. I. Försönits, G. Petővári, A. Sebestyén, Z. Komlósi, L. Drahos, Á. Kittel, G. Nagy, A. Bácsi, Á. Dénes, Y. S. Gho, K. É. Szabó‐Taylor, E. I. Buzás, J Extracell Vesicles 2021, 10, e12140.
L. Dietz, J. Oberländer, A. Mateos‐Maroto, J. Schunke, M. Fichter, E. M. Krämer‐Albers, K. Landfester, V. Mailänder, J Extracell Vesicles 2023, 12, e12399.
M. Heidarzadeh, A. Zarebkohan, R. Rahbarghazi, E. Sokullu, Cell Commun Signal 2023, 21, 64.
S. Mayor, R. E. Pagano, Nat. Rev. Mol. Cell Biol. 2007, 8, 603.
L. A. Mulcahy, R. C. Pink, D. R. Carter, J Extracell Vesicles 2014, 3, 24641.
H. Costa Verdera, J. J. Gitz‐Francois, R. M. Schiffelers, P. Vader, J Control Release 2017, 266, 100.
L. Wu, L. Wang, X. Liu, Y. Bai, R. Wu, X. Li, Y. Mao, L. Zhang, Y. Zheng, T. Gong, Z. Zhang, Y. Huang, Acta Pharm. Sin. B 2022, 12, 2029.
J. Lu, X. Shen, H. Li, J. Du, Exploration 2024, 20230142.

2021YFA1201000 National Key Research & Development Program of China; 32030060 NSFC key project; 82202336 National Natural Science Foundation of China; 51861135103 international collaboration key project; 121D11KYSB20210003 Chinese Academy of Sciences; 2021A1515110619 Guangdong Basic and Applied Basic Research Foundation; 2023YFC2605000 National Key R&D Program of China

Keywords: cryogenic freezing; gastrointestinal barrier; isolation method; milk‐derived extracellular vesicles; oral delivery

Date Created: 20240520 Date Completed: 20241028 Latest Revision: 20241028

20241029

10.1002/adhm.202401370

38767497