Extracellular vesicles (EVs) are nano-sized membrane vesicles, released by many cell types. The cargo of EVs comprises small and long, coding and non-coding RNAs, lipids and proteins. EVs could be transferred between cells, and alter the recipient cells phenotype. In addition, through their important role in intercellular communication, EVs affect various processes involved in health and disease. EVs make up a natural mechanism for information transfer between cells and have the potential as a new drug delivery platform. Creative Biolabs is dedicated to providing the best-quality EV surface engineering services for our customers.
EVs have been observed in all body fluids, such as blood, urine, saliva, sputum, breast milk, semen, and cerebrospinal fluid. Cells can release distinct types of EVs, including exosomes, microvesicles, and apoptotic bodies. The method of collecting EVs include ultracentrifugation, density gradient centrifugation, filtration and size-exclusion chromatography. EVs is an ideal carrier system and has many features. EVs possess intrinsic cell targeting properties, and are able to overcome natural barriers such as the blood-brain barrier. Furthermore, EVs likely utilize endogenous mechanisms for uptake, intracellular trafficking and subsequent delivery of their content in recipient cells. Importantly, EVs may be nearly non-immunogenic when used autologously.
Fig.1 Advantages of displaying membrane proteins on the surfaces of EVs. (Yang, 2018)
1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR)-labeled EVs from various cell sources was investigated to overcome issues of unfavorable pharmacokinetics and lack of selectivity. Furthermore, cell source, EV dose, and route of administration affect EV distribution, which may have implications for the design and feasibility of therapeutic studies using EVs.
Intranasal administration of mouse lymphoma EVs loaded with the anti-inflammatory drug curcumin localize to the brain. Curcumin levels peaked at 1 hour after administration, and a significant amount could still be detected after 12 hours. For therapeutic applications, local drug administration may be preferred, when targeting the central nervous system.
The lipid bilayer membrane serves as a natural barrier to protect EV cargo from degradation in the bloodstream. We provide two different loading approaches. One approach is based on the loading of therapeutics into cells from which the EVs are derived, which, using the endogenous loading machinery of the cells, may result in subsequent EV loading with the drug of interest. The second approach involves the loading of EVs after their isolation.
Fig.2 Animated overview of EV loading strategies. (Vader, 2016)
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