Exosome as a stable carrier for anti-inflammatory phenylpropanoid metabolites: a proof-of-concept study

Phenylpropanoids (PA), which are plentiful in cruciferous vegetables, have not received adequate attention for their anti-inflammatory properties. Despite their potential benefits, the bioavailability and stability of these and other natural compounds under physiological conditions remain limited. This study aims to develop a natural nanovesicular delivery system that efficiently incorporates a phenylpropanoid extract-specifically, a multi-component anti-inflammatory extract derived from broccoli-with the goal of enhancing its bioavailability. This initiative serves as proof of concept for further research and application. The findings suggest that phenylpropanoids (PAs) achieve a 75% encapsulation efficiency within exosomes. Furthermore, it has been observed that PAs encapsulated in exosomes demonstrate a stability that is twice that of unencapsulated PAs under physiological conditions. The encapsulation process also improved the cytocompatibility of the PAs. Moreover, the functionality of the encapsulated PAs is significantly improved, as evidenced by a fivefold reduction in nitric oxide production from the EXO/PA nanocarriers. There is a significant decrease in the expression of pro-inflammatory genes, such as NFkB, MMP2, COX-2, and IL-1β, in comparison to cells treated with LPS. Moreover, levels of TNF-α, IL-6, and MCP-1 in activated macrophages treated with EXO/PAs were observed to be significantly reduced compared to those activated by LPS. It appears that the immune-suppressive effect of the extract may be mediated through both the ERK/MAPK and IkB/NFkB signaling pathways, highlighting the potential benefits of this approach. In conclusion, the results demonstrate that exosomes can effectively deliver polyphenylpropanoids while improving their stability and functionality, underscoring their potential role in future medical treatments.