Biodistribution and Pharmacokinectics of Liposomes and Exosomes in a Mouse Model of Sepsis

Abstract

Exosomes have attracted considerable attention as drug delivery vehicles because their biological properties can be utilized for selective delivery of therapeutic cargoes to disease sites. In this context, analysis of the in vivo behaviors of exosomes in a diseased state is required to maximize their therapeutic potential as drug delivery vehicles. In this study, we investigated biodistribution and pharmacokinetics of HEK293T cell-derived exosomes and PEGylated liposomes, their synthetic counterparts, into healthy and sepsis mice. We found that biodistribution and pharmacokinetics of exosomes were significantly affected by pathophysiological conditions of sepsis compared to those of liposomes. In the sepsis mice, a substantial number of exosomes were found in the lung after intravenous injection, and their prolonged blood residence was observed due to the liver dysfunction. However, liposomes did not show such sepsis-specific effects significantly. These results demonstrate that exosome-based therapeutics can be developed to manage sepsis and septic shock by virtue of their sepsis-specific in vivo behaviors.

Biodistribution of Exosomes and Engineering Strategies for Targeted Delivery of Therapeutic Exosomes

“…Whereas this review paper is mainly focused on exosomes, readers can find recent advances regarding other EVs, such as microvesicles, on review papers cited here [12,26]. Focusing on exosome therapeutics, the major tissues distribution of systemically administered exosomes generally include liver, spleen, kidney, lung and gastrointestinal tract, which can be altered by various factors such as cellular origin of exosomes, exosomal membrane composition (e.g., protein, lipid, and glycan) and pathophysiological condition of host [27][28][29][30][31][32][33][34][35]. Exosome engineering for targeted delivery of therapeutic exosomes to various tissues including brain, placenta, heart, spinal cord, and cartilages is also being investigated [36][37][38][39][40][41].…”

“…They found that substantial number of exosomes were delivered to the lung compared to healthy mouse after intravenous injection, of which more than 30% of exosomes were delivered to the lung in sepsis-induced mouse after 1 h of injection whereas almost none were detected in the lung of healthy mouse. Also, prolonged retention of exosomes in the blood circulation were observed due to liver dysfunction [ 28 ]. In other disease models, clearance of fluorophore labeled exosomes (10 nmol, intravenous) from blood in normal mice were 0.0054–0.0154 mL/min [ 67 ], whereas Gaussia luciferase (gLuc)-lactadherin (LA) labeled exosomes (5 µg, intravenous) in macrophage-depleted mice [ 42 ] and 125 I labeled exosomes (4 × 10 5 cpm, intravenous) in Parkinson’s disease mouse model [ 65 ] were 0.651 ± 0.157 mL/h and 0.016 mL/min, respectively.…”

Potential Applications and Functional Roles of Exosomes in Cardiometabolic Disease

“…Evidence shows that renal excretion may not contribute to the rapid clearance of EVs from circulation [38]. However, biliary excretion and renal clearance of exosomes have been observed as soon as 5 h after administration [43].…”

“…Exosomes from different cell types have shown an asymmetric biodistribution [42]. Furthermore, the biodistribution and retention of exosomes in a particular tissue can be influenced by pathophysiological processes [43]. In this regard, exosome surface modifications have allowed the attachment of different moieties for targeted drug delivery.…”

Sustained Released of Bioactive Mesenchymal Stromal Cell-Derived Extracellular Vesicles from 3D-Printed Gelatin Methacrylate Hydrogels

“…The abilities of MSC EVs to deliver bioactive macromolecular cargo to recipient cells as well as their more drug-like qualities as compared to whole cell-based therapies make MSC EVs especially attractive for tissue repair and regeneration. However, EVs in general are also characterized by relatively rapid clearance from the blood after systemic delivery [14][15][16],…”