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《2018年第十二届中国药物制剂大会论文集》2018年
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Macrophage membrane coated ROS-responsive nanoparticles for the treatment of atherosclerosis

高成  Qiaoxian Huang  Chonghui Liu  Simon M.Y.Lee  Ruibing Wang  
【摘要】:Selected drug release to targeted tissues has been one of the most challenging tasks in drug delivery, which, if works as expected, would improve therapeutic efficacy and reduce side effects. In reality, the amount of drug released in targeted tissue is often far from adequacy, as most of the drugs are usually metabolized or eliminated during blood circulation before reaching targeted tissue.1 Recently, a variety of stimuli-sensitive drug delivery systems exhibiting selective drug release behaviors in response to the microenvironment in the specific tissues have been developed, however, few of these materials are able to achieve ideal targeting efficiency2. Herein, we report macrophage cell membrane coated ROS responsive nanoparticles(MM-NPs) based on oligochitosan. On the one hand, the membrane of immune cells significantly lowered the immunogenicity of the NPs and contributed to the targeted drug transport to inflammatory tissues where a high level of ROS is present. On the other hand, after reaching the targeted inflammatory tissue, the ROS sensitive NPs were broken apart and the encapsulated therapeutic payload was released in response to the high level of ROS. Transmission electron microscope(TEM) and dynamic light scattering(DLS) analysis exhibited a uniform nanosphere and good stability in PBS and cell culture medium. In vitro drug release profiles of the MM-NPs under various ROS conditions as well as in ROS-generating cellular model exhibited decent ROS-responsiveness. Furthermore, atorvastatin loaded NPs(MM-AT-NPs) improved the cell viability and lowered apoptosis rates of macrophage treated by lipopolysaccharide(LPS), similar to those treated by free AT. The NO level and inflammatory cytokines were also attenuated on LPS treated macrophages by MM-AT-NPs. Finally, in vivo experiment on mouse showed significantly improvement on the accumulation of MM-NPs at the site of atherosclerosis in comparison to free drug and ROS responsive NPs. In summary, this cell membrane coated ROS-responsive NP platform exhibited more efficient targeted delivery in comparison with ROS-responsive NPs without membrane-coating, and may offer a new avenue for clinical treatment of inflammatory diseases such as atherosclerosis.

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