Mare’s milk-derived exosomes for polyphenols delivery

Collaborative Research Program 2021-2023

Project goal: to establish the possibility of using exosomes obtained from a specific national food product of Kazakhs, mare’s milk, as a transport system to increase the bioavailability of plant polyphenols using quercetin as an example. The main hypothesis that will be tested in this project: exosomes obtained from mare’s milk, a traditional type of dairy farm animal in Kazakhstan, can be a transport system to increase the bioavailability of plant polyphenols after ingestion. It is known that extracellular vesicles (30–160 nm), called exosomes, are present in the milk of farm animals [1,2]. Milk-derived exosomes have been characterized as relatively stable vesicles [3]. Milk-derived exosomes have been shown to contain miRNAs, such as miRNA-148a-3p [4]. It has been found that exosomes can invade cells, and they can regulate biological and cellular functions, such as gene expression [3,5]. The transport function of exosomes is especially intensively studied. Exosomes are biological nanovesicles that are involved in cell-cell communication via the functionally-active cargo (such as miRNA, mRNA, DNA and proteins). Because of their nanosize, exosomes are explored as nanodevices for the development of new therapeutic applications. Extracellular vesicles (Exosomes) were first described by Trams et al. in 1981 as cell-secreted particles that carried membrane-bound enzymes, and could be taken up by recipient cells [6]. The authors keenly predicted that EVs could represent an important pathway to transfer information between cells and might be developed to package and deliver therapeutic molecules like structurally similar liposomes. Although exosomes are not nanoparticles derived from the nanotechnology due to its non-mankind nature, they may act as a nanocarrier owing to their particle diameter. Therefore, exosome’s particle size resulting in deep penetration into the tissues and overcoming barriers such as the blood-brain barrier and the deformable cytoskeleton [7]. Notably, they have slightly negative zeta potential that guarantees their long circulation [8]. In addition, some exosomes are capable of escaping from the immune system and have shown low immunogenicity and high stability in the blood, which prolongs the circulation of the drug within the body [9]. Furthermore, exosomes can be employed to load a variety of small bioactive molecules as a nanocarrier. Since bovine milk exosomes are protected from degradation by stomach acids [2,10], milk exosomes are, therefore, considered to be useful for drug-delivery systems (DDSs) in human medicine; milk exosome-encapsulated formulations can be used for therapeutic purposes [11]. Therefore, milk-derived exosomes are seen as promising new drug carriers for reaching distant tissues [12,13]. Best characterized by milk-derived exosomes from cow's milk [14].