Tailored platelet biomimetic delivery platform for targeted therapy of inflammatory bowel disease

Abstract

Effective delivery of drugs to the inflamed colon is an attractive strategy for treating inflammatory bowel disease (IBD). Here we designed a drug delivery platform for IBD treatment by hybridizing platelet membrane (PM) with phosphatidylserine (PS)-containing liposomes (PM-Lipo). Introducing PM into hybrid nanovesicles enhanced their adhesion to the inflammatory endothelium in vitro, and increased their recruitment to the inflamed colon in a mouse IBD model. Meanwhile, adding PS into PM-Lipo improved macrophage targeting and uptake in vitro and in vivo. Rosiglitazone (ROSI) loading PM-Lipo (PM-Lipo-ROSI) effectively reprogrammed the pro-inflammatory macrophages towards an anti-inflammatory status in the inflamed colon, reducing pro-inflammatory cytokine secretion and immune cell infiltration. Moreover, PM-Lipo-ROSI also promoted the epithelial barrier regeneration of the damaged colon. The present study not only provides a novel paradigm for the precision treatment of IBD, but also lays a theoretical foundation for developing nanomedicines for other inflammatory diseases.