Neutrophil Membrane-Coated Mesoporous Silica Nanoparticles Loaded with Hydrocortisone Alleviate DSS-Induced Colitis in Mice

Abstract

The incidence and prevalence of ulcerative colitis (UC) are increasing worldwide. Hydrocortisone enema (HC) is widely used in UC treatment; however, this approach is limited by the easy degradation of HC in the intestinal environment and low intestinal uptake efficiency. Accordingly, the development of methods to improve the targeting efficiency of corticosteroids is an important issue. Mesoporous silica nanoparticles (MSN) and biomimetic nanovesicles (derived from the natural cell membrane structure) provide a basis for improved drug delivery and uptake. In this research, we constructed neutrophil membrane-coated MSN loaded with HC for the treatment of UC. MSN-HC and neutrophil-derived membrane nanoparticles (MSN-HC@NM NPs) were obtained by mechanical extrusion and characterized. The effects of free HC, MSN, MSN-HC, and MSN-HC@NM NPs were compared using dextran sodium sulfate (DSS)-induced colitis model, including terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays and inflammatory factors in colon tissues. The MSN-HC@NM NPs alleviated DSS-induced colitis by reducing colon apoptosis and ameliorating the destruction of the colonic barrier and inflammation in mice. This research provides a hydrocortisone delivery system with good biosafety and the potential for clinical translation.