Therapeutic Potential of Milk-derived Extracellular Vesicles as Drug Delivery System

Abstract

drug delivery in a multitude of disease models. mEVs present in milk are derived from mammary cells and are hypothesized to comprise exosomes, microvesicles, and apoptotic bodies. mEVs effectively deliver their content, consisting of different biological components, including protein, RNA, and lipids, to recipient cells. The function of mEVs is dependent on their exact content, but several beneficial effects have been attributed to mEVs, including immunoregulatory and anti-tumour effects. This, in combination with the delivery potential of mEVs, makes them a suitable candidate for the development of novel delivery systems for therapeutics. Moreover, mEVs have been found to resist degradation in the gastro-intestinal tract and blood circulation, hinting towards the possibility of oral and intravenous administration. These properties seem to persist cross-species, meaning that mEVs can be derived from a cost-effective and widely available source in the form of bovine milk. In addition, it has been shown that modification of mEV lipid bilayers enables specific targeting of disease tissue, adding to the therapeutic potential of mEVs. Although the development of mEV drug carriers is promising, considerations need to be made before therapeutic applications can be realised. This review aims to provide an overview of the current state of knowledge on mEV characteristics in relation to their potential as drug delivery systems and to discuss practical considerations in the process of developing such a system. To this end, the current methods for isolation and drug loading were evaluated and coupled to the biodistribution of mEVs. Finally, recent developments in mEV therapies for cancer and other diseases were discussed, as well as considerations for future perspectives. It was concluded that improvements in scalability and standardisation of isolation and characterisation methods need to made in order for clinical application to be realised. Moreover, mEV functions, their mechanism of action, and biodistribution need to be elucidated for the development of a safe drug delivery system. Lastly, methods used in industrial processing, isolation, loading, and administration can reduce mEV integrity, but further in vivo studies are required to determine the degree of reduction in functionality.