Bioavailability of orally administered small extracellular vesicles from bovine milk in C57BL/6J mice. 2023

Afsana Khanam, and Alice Ngu, and Janos Zempleni
Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, 316 Leverton Hall, Lincoln, NE 68583-0806, USA.

Small extracellular vesicles (sMEVs) from bovine milk are studied for delivering therapeutics. Here, we estimated sMEV bioavailability of an oral dose of sMEVs. Bovine sMEVs were labeled covalently with HiLyteTM 750 (MEV-750) and administered by oral gavage to C57BL/6J mice. Plasma, urine, feces, and tissues were harvested at timed intervals for up to 24 h and fluorescence was assessed. Fecal excretion amounted to approximately 55% of the oral MEV-750 dose in males and females. The levels of MEV-750 peaked in the intestinal mucosa and plasma approximately 6 h after oral gavage and returned to baseline at time point 24 h. MEV-750 were detectable in peripheral tissues approximately 12 h after gavage. MEV-750 excretion in urine peaked approximately 6 h after oral gavage and returned to background levels after 24 h. Analysis by size exclusion chromatography suggested that HiLyteTM detached from sMEVs in artificial gastric fluid but not in plasma, i.e., HiLyteTM allows to estimate sMEV bioavailability with comparably high confidence. We conclude that the apparent bioavailability of sMEVs is 45%, and sMEVs are transported to peripheral tissues in C57BL/6J mice; excretion in feces and urine are the main routes of sMEV elimination.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008892 Milk The off-white liquid secreted by the mammary glands of humans and other mammals. It contains proteins, sugar, lipids, vitamins, and minerals. Cow Milk,Cow's Milk,Milk, Cow,Milk, Cow's
D001826 Body Fluids Liquid components of living organisms. Body Fluid,Fluid, Body,Fluids, Body
D005243 Feces Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
D005260 Female Females
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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