Journal
JOURNAL OF CONTROLLED RELEASE
Volume 316, Issue -, Pages 236-249Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2019.10.043
Keywords
Apoptotic body; Atherosclerosis; Liposomes; Macrophages; Pioglitazone
Funding
- National Natural Science Foundation of China [81773664, 81473153, 81503006, 3100877]
- Natural Science Foundation of Jiangsu Province [BK20150698, BK20170747]
- National Basic Research Program of China [2015CB755504]
- 111 Project from the Ministry of Education of China [111-2-07, B17047]
- State Administration of Foreign Expert Affairs of China [111-2-07, B17047]
- Open Project of State Key Laboratory of Natural Medicines [SKLNMZZCX201811]
- Double First-Class University project [CPU2018GF10]
- Opening Project of Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (Sichuan University)
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The macrophages mediated inflammation participates in every stage of atherosclerosis. Attenuation of macrophages inflammatory responses by active ingredients in atherosclerotic plaques is benefit to atherosclerotic stabilization and regression, but meanwhile, it is highly desired to develop accurate therapeutics for reducing off-target effects. Previous studies revealed that the apoptotic bodies are effectively recognized and engulfed by macrophages own to increased exposure of phosphatidylserine (PtdSer), which is regarded as a key eat-me signal. To achieve optimal delivery efficiency, an apoptotic body biomimic liposome (AP-Lipo) is constructed by decorating PtdSer and DSPE-PEG2000-cRGDfK onto the surface of liposome for selectively delivering pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, into atherosclerotic macrophages while minimizing its side effects. Compared with unmodified liposome, AP-Lipo is more effective to recognize and penetrate the activated vascular endothelial monolayer, target pro-inflammatory macrophages and suppress the inflammation by upreglation of anti-inflammatory cytokines in vitro. Moreover, AP-Lipo can effectively target to atherosclerotic plaques and imped the progression of atherosclerosis by upregulating anti-inflammatory macrophages number and stabilizing the atherosclerotic plaques. In summary, this design imitates the characteristic of apoptotic body and provides a potential drug delivery system for atherosclerosis and other diseases, which attribute to inflammation mediated by macrophages.
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