Low molecular weight fucoidan modified nanoliposomes for the targeted delivery of the anti-inflammation natural product berberine

[Display omitted] The inflammatory response is the basis of many diseases, such as atherosclerosis and ulcerative colitis. Inhibiting inflammatory response is the key to treating these diseases. Berberine hydrochloride (BBR), a natural product, has shown effective inflammation inhibitory activity. However, its distribution throughout the body results in a variety of serious side effects. Currently, there is a lack of targeted delivery systems for BBR to inflammatory sites. In view of the fact that the recruitment of inflammatory cells by activated vascular endothelial cells is a key step in inflammation development. Here, we design a system that can specifically deliver berberine to activated vascular endothelial cells. Low molecular weight fucoidan (LMWF), which can specifically bind to P-selectin, was coupled to PEGylated liposomes (LMWF-Lip), and BBR is encapsulated into LMWF-Lip (LMWF-Lip/BBR). In vitro, LMWF-Lip significantly increases the uptake by activated human umbilical vein endothelial cells (HUVEC). Injection of LMWF-Lip into the tail vein of rats can effectively accumulate in the swollen part of the foot, where it is internalized by the characteristics of activated vascular endothelial cells. LMWF-Lip/BBR can effectively inhibit the expression of P-selectin in activated vascular endothelial cells, and reduce the degree of foot edema and inflammatory response. In addition, compared with free BBR, the toxicity of BBR in LMWF-Lip/BBR to main organs was significantly reduced. These results suggest that wrapping BBR in LMWF-Lip can improve efficacy and reduce its systemic toxicity as a potential treatment for various diseases caused by inflammatory responses.