Figure 1.

Sources of exosomes and design of biomimetic vehicles. Purposes of inoculation routes are (1) minimizing invasiveness, (2) targeting cell-specific (i. e., gut or beta pancreatic cells) or tissue-specific delivery (i. e., brain). (A) Engineered cells for producing exosomes. (B) Nanoliposomes produced from living cells. (C) Lipid nanoparticles & Niosomes (Diameter between 10–100 nm, made with non-ionic surfactants including alkyl esters, ethers, and amides.). Most applications are targeting T lymphocytes or dendritic cells. Beside these attempts to mimic more or less closely natural exosomes, amphiphilic lipids made of aminoglycosides rings (D) are also used to deliver nucleic acid in target cells, the main application being vaccination. Mechanism of cytosol delivery has been studied under electron microscopy (23). Moreover, oral inoculation opens the possibility to target digestive epithelial cells (24). Note that blood-brain barrier at the plexus choroid can relay signal received from circulating exosomes by producing de novo exosomes liberated in brain area (25). A cellular target could be pancreatic beta-cells, the cell surface proteome has been described (26) opening the way to specifically address biodesigned nanoparticles loaded with miRNAs. Patients undergoing bariatric surgery are frequently recovering from type-2 diabetes, strongly suggesting that gastrointestinal epithelium is crucial in such pathology and opening the way for treating metabolic diseases by oral delivery of drugs (27).