Oral delivery of layer-by-layer coated exosomes for colitis therapy.

Mesenchymal stem cell-derived exosomes (MSC-Exos) have attracted much attention as a potential cell-free therapy for ulcerative colitis (UC), mainly due to their anti-inflammatory, tissue repair, and immunomodulatory properties. Although intravenous injection of MSC-Exos is able to improve UC to a certain extent, oral administration of exosomes is the preferred method to treat gastrointestinal diseases such as UC. However, exosomes contain proteins and nucleic acids that are vulnerable to degradation by the gastrointestinal environment, making oral administration difficult to implement. Layer-by-layer (LbL) self-assembly technology provides a promising strategy for the oral delivery of exosomes. Therefore, an efficient LbL-Exos self-assembly system was constructed in this study for the oral delivery of exosomes targeted to the colon to improve UC treatment. Biocompatible and biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) and oxidized konjac glucomannan (OKGM) polysaccharides were used as the outer layers to provide colon targeting and to protect exosomes from degradation. Similar to plain exosomes, LbL-Exos had a similar structure and features, but LbL provided controlled release of exosomes in the inflammatory colon. Compared with intravenous administration, oral administration of LbL-Exos could effectively alleviate UC using half the number of exosomes. Mechanistic studies showed that LbL-Exos were internalized by macrophages and intestinal epithelial cells to exert anti-inflammatory and tissue repair effects and therefore alleviate UC. Furthermore, the LbL-Exos system was able to improve UC via MAPK/NF-κB signaling pathway inhibition. Overall, our data show that LbL-MSC-Exos can alleviate UC after oral administration and therefore may constitute a new strategy for UC treatment in the future.

Self-assembled micelle derived from pterostilbene ameliorate acute inflammatory bowel disease.

PEGylated pterostilbene micelle (PTENPs) with higher bioavailability, biocompatibility, and water solubility were prepared. Then we detected the therapeutic effects in the treatment of inflammatory bowel disease (IBD), together with its potential mechanisms. The anti-oxidant effects and anti-inflammatory effects of PTENPs were determined under in vitro and in vivo conditions. Besides, the cellular toxicity of the PTENPs was determined in vitro, and biocompatibility testing was performed on a colitis mice model to determine its safety. The self-assembled PTENPs showed potency in treating IBD, which was featured by effectively anti-oxidant capacity, inhibition of cellular damages, and an anti-inflammatory role. In addition, PTENPs could inhibit the activation of TLR4, thereby inhibiting the NF-κB and MAPK signaling pathways. Meanwhile, it could protect colonic tissues from oxidative damage, which promoted the remission of colonic inflammation with low toxicity. Compared with free PTE, PTENPs could effectively ameliorate acute IBD with low toxicity, which may be related to the inactivation of TLR4, and inhibition of NF-κB and MAPK signaling pathways.

Human placental mesenchymal stem cell derived exosomes exhibit anti-inflammatory effects via TLR4-mediated NF-κB/MAPK and PI3K signaling pathways.

Exosomes are a type of nanoparticles in 40-200 nm extracellular vesicles secreted from living cells, containing a plurality of biologically active substances, which can be used as carriers of intercellular delivery signals. Among them, mesenchymal stem cell (MSC)-derived exosomes have been reported to play important roles in injury repair, alleviating inflammation; thus, MSC-derived exosomes have become hot spot in noncellular therapies. The role of human placental MSC-derived exosomes (hplMSC-Exos) in inflammation and their potential mechanisms are unclear. Therefore, we investigated the anti-inflammatory effects of hplMSC-Exos in lipopolysaccharide (LPS)-induced RAW264.7 cells and their intrinsic mechanisms. Our data demonstrated that hplMSCs-Exos can adjust inflammation by regulating TLR4-mediated NF-κB/MAPK and PI3K signaling pathways, indicating that hplMSCs-Exos can act as a new strategy for inflammatory treatment.