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Review: Milk Small Extracellular Vesicles for Use in the Delivery of Therapeutics

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Abstract

Small extracellular vesicles (sEVs, “exosomes”) in milk have attracted considerable attention for use in delivering therapeutics to diseased tissues because of the following qualities. The production of milk sEVs is scalable, e.g., more than 1021 sEVs may be obtained annually from a single cow. Milk EVs protect their cargo against degradation in the gastrointestinal tract and during industrial processing. Milk sEVs and their cargo are absorbed following oral administration and they cross barriers such as intestinal mucosa, placenta and the blood–brain barrier in humans, pigs, and mice. Milk sEVs do no alter variables of liver and kidney function, or hematology, and do not elicit immune responses in humans, rats, and mice. Protocols are available for loading milk sEVs with therapeutic cargo, and a cell line is available for assessing effects of milk sEV modifications on drug delivery. Future research will need to assess and optimize sEV shelf-life and storage and effects of milk sEV modifications on the delivery of therapeutic cargo to diseased tissues.

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Abbreviations

ESCRT:

Endosomal complex required for transport

EV:

Extracellular vesicle

MVB:

Multivesicular body

sEV:

Small EV

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Funding

This work was supported by the National Institutes of Health (P20GM104320 and OD028749), the National Institute of Food and Agriculture (2016–67001-25301, 2020–67017-30834, and 2022–67021-36407), the U.S. Department of Agriculture (Hatch, and W-4002) and the SynGAP Research Fund (all to J. Zempleni).

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Authors and Affiliations

  1. Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, 1700 N. 35 Street, 316C Leverton Hall, Lincoln, Nebraska, 68583, USA

    Javaria Munir, Alice Ngu, Haichuan Wang & Janos Zempleni

  2. Department of Neurology, Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Denise M. O. Ramirez

  3. Peter O’Donnell, Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Denise M. O. Ramirez

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  1. Javaria Munir
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  2. Alice Ngu
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  3. Haichuan Wang
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  4. Denise M. O. Ramirez
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  5. Janos Zempleni
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Contributions

J. Zempleni wrote the draft version and final manuscript and prepared the figures. J. Munir, Alice Ngu, H. Wang, and Denise M. O. Ramirez have revised the draft version critically for important intellectual content. All authors have read and approved the final version of the manuscript, and have agreed to be accountable for all aspects of this work.

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Correspondence to Janos Zempleni.

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J. Zempleni is a consultant for PureTech Health, Inc. (Boston, MA). The authors declare no conflicts of interest.

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Munir, J., Ngu, A., Wang, H. et al. Review: Milk Small Extracellular Vesicles for Use in the Delivery of Therapeutics. Pharm Res 40, 909–915 (2023). https://doi.org/10.1007/s11095-022-03404-w

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  • DOI: https://doi.org/10.1007/s11095-022-03404-w

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