Methyl gallate-loaded platelet-mimetic liposome for targeted therapy of ulcerative colitis.

Abstract

Ulcerative colitis (UC) is a persistent inflammatory bowel disease that poses an increasingly significant public health concern worldwide. Given the limited efficacy of current therapies, the development of novel treatment approaches has become increasingly urgent. Our previous investigation established that methyl gallate (MG) exhibits therapeutic potential for UC due to its effective anti-inflammatory properties. However, the low targeting specificity and high in vivo clearance rate of MG restrict its application. Herein, platelet membrane (PM) biomimetic MG-loaded liposome (PML) was firstly constructed to improve MG delivery and enable targeted UC therapy. Due to the PM cloaking, PML exhibited prolonged circulation time and enhanced targeting to damaged colon caused by UC. Moreover, the PM biomimetic liposome demonstrated higher uptake efficiency in inflammatory cells. In vitro and in vivo investigations consistently proved that PML exhibited significant anti-inflammatory activity. Additionally, intravenous administration of PML effectively reduced disease severity in UC mouse models and promoted the intestinal tissue repair. Besides, PML showed high erythrocyte compatibility and favorable biosafety in UC mice and zebrafish. Collectively, PML achieve enhanced MG delivery and may provide a novel precision therapy strategy for UC treatment.