Abstract
Inflammatory bowel disease(IBD)is a refractory chronic intestinal inflammatory disease caused by a mal-function of immune system.As the key immune cells in the intestine,macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD.Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD.In this study,mannose-modified liposomes(MAN-LPs)are prepared for macrophage targeting to improve therapeutic efficiency.Rosiglita-zone(ROSI)as an agonist of peroxisome proliferators-activated receptor y(PPAR-y)is used as the model drug to fabricate different sized liposomes.The impacts of mannose modification and particle size for macrophage targeting are investigated in cells,zebrafish,and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium(DSS)-induced IBD mouse.Compared to un-modified liposome,MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model.Furthermore,MAN-LPs could effectively accumulate in the inflamma-tory intestinal sites in IBD mouse model.Most importantly,the targeting ability of MAN-LPs is obvi-ously enhanced with the increasing of particle size,whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells,and a higher therapeutic efficiency in IBD mouse model.Therefore,mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment.Particle size of MAN-LPs will affect macrophage targeting ability,as well as the therapeutic effect in-vivo.
基金项目
Macau Science and Technology Development Fund(0086/2021/A2)
Shenzhen Fundamental Research Program(SGDX20210823103804030)
Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macau Joint Lab)(2020)(2020B1212030006)
Guangdong Basic and Applied Basic Research Foundation(2022A1515012416)
NETL
NSTL
维普
万方数据