Table 5.
Administration routes used for EV drug delivery
| Administrative route |
EV source | Biodistribution of EVs |
Cargo/modification | Purpose | Reference |
|---|---|---|---|---|---|
| Intranasal | |||||
| Tumor cells | Microglial cells | Curcumin | Treatment of LPS- induced brain inflammation | (Zhuang et al., 2011) | |
| Macrophages | Throughout the brain | Catalase | Drug delivery for Parkinson’s disease | (Haney et al., 2015) | |
| Astrocytes | Heart, lung,brain,liver, Gut. Microglial cells | si-LincRNA-COX2 | Block morphine-mediated impairment of microglial phagocytosis | (Hu et al., 2018) | |
| Macrophages | N/A | M. tuberculosis lipoprotein, culture filtrate proteins | Decreased growth of M. tuberculosis in the lung | (Cheng and Schorey, 2013) | |
| Intravenous | |||||
| Mesenchymal stem cells (MSCs) | Liver, brain and spleen | Near-infrared (NIR) dye (DiD) labeling | Targeting acute kidney injury | (Grange et al., 2014) | |
| MSCs | Cardiac cells | Unmodified | Decrease Myocardial ischemia/reperfusion injury | (Arslan et al., 2013) | |
| MSCs | Lung vascular cells | Unmodified | Decreased lung inflammation and hypoxia-induced hypertension | (Lee et al., 2012) | |
| ESC-derived MSCs | Cardiac cells | Unmodified | Reduced myocardial infarct size and inflammation | (Arslan et al., 2013) | |
| HEK293 | HCC70 cells > HCC1954 or MCF-7 cells (EGFR- dependent mechanism) | GE11- or EGF- positive exosomes | Tumor targeting | (Ohno et al., 2013) | |
| HEK293 | Liver, spleen and plasma | Heterodimeric cytokine complex Interleukin-15: Interleukin-15 receptor alpha | Efficient production and enhanced tumor delivery | (Watson et al., 2016) | |
| Dendritic cells (DCs) | Brain | Lamp2b fused to the neuron-specific RVG peptide | Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. | (Alvarez- Erviti et al., 2011) | |
| DCs | Human breast cancer cell line MDA-MB-231(αv integrin- dependent machanism) | Doxorubicin-loaded EVs from DCs expressing iRGD | Decreased tumor growth compared to free doxorubicin or untargeted EVs | (Tian et al., 2014) | |
| Breast cancer 4T1 cell line | Tumor, liver and Intestine | pCMV-luc2/miR-210 | Visualization of exosome-mediated miR-210 transfer | (Jung et al., 2017) | |
| 293T | Spleen >Liver >Lung and Kidney> Brain, heart and muscle | Gaussia luciferase and biotin on the surface of EVs | Dynamic biodistribution | (Lai et al., 2014) | |
| Intracardiac | |||||
| Cardiac progenitor cells | H9C2 cardiomyoblasts | GATA4-responsive-miR-451 | Inhibited cardiomyocyte apoptosis | (Chen et al., 2013) | |
| Cardiosphere-derived cells | Cardiomyocyte, HUVEC | miR-146a | Cardiac regeneration | (Ibrahim et al., 2014) | |
| GATA-4 overexpressing MSCs | Myocardium ischemic boarder area | miR-19a | Cardioprotective capabilities of exosomes | (Yu et al., 2015) | |
| Intraperitoneal | |||||
| HEK293 | Tumor tissue | IL3-Lamp2b EVs loaded with Imatinib or with BCR-ABL siRNA | Inhibits Chronic Myelogenous Leukemia cell growth | (Bellavia et al., 2017) | |
| MSCs | N/A | Unmodified | Postischemic Immunosuppression | (Doeppner et al., 2015) | |
| Intramuscular | |||||
| MSCs | SVEC4 endothelial cells | VEGF protein and miR-210–3p | Accelerated recovery of hindlimb ischemia | (Gangadaran et al., 2017) | |
| Adipose stem cells | Adipose stem cells (ASCs) | Ultrasmall superparamagnetic iron oxide nanoparticles | New approach for labeling of exosomes that allows detection by MRI | (Busato et al., 2016) | |
| Intradermal | |||||
| MSCs | Lung, liver and kidney DP cells | DiD-labeled MSC- EVs | Dermal papilla activation | (Rajendran et al., 2017) | |
| Footpad | |||||
| Mouse B16-F10 melanoma cells | N/A | Superparamagnetic iron oxide nanoparticles | Magnetic resonance imaging of melanoma exosomes in lymph nodes | (Hu et al., 2015) | |
| Bone marrow- derived DCs | CD11c+ cells | FasL | Inhibit the progression of established collagen-induced arthritis (CIA) | (Kim et al., 2006) | |
| Oral | |||||
| Grape juice | Intestinal stem cells | Unmodified | Decreased colitis-induced colon shrinkage and mortality | (Ju et al., 2013) | |
| Subcutaneous | |||||
| Splenic DCs | N/A | Toxoplasma gondii-derived antigens | Fewer T. gondii cysts in mother and pup brains, increased pup survival | (Beauvillain et al., 2009) | |
| Multiple | |||||
| Intravenous Intracardiac | Lung, liver & brain tumor cells, breast and pancreatic cancer cells | Lung and liver | Exosomal integrins α6β4, α6β1 and αvβ5 | Organotropic metastasis | (Hoshino et al., 2015) |
| Intravenous Intratumor | Breast cancer cell lines | Liver, spleen and kidneys | Unmodified | Biodistribution and delivery efficiency | (Smyth et al., 2015) |