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作 者:Yumei Wang Jia Ke Xianmou Guo Kaijun Gou Zhentao Sang Yanbu Wang Yan Bian Sanming Li Heran Li
机构地区:[1]Department of Pharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,China [2]School of Pharmacy,China Medical University,Shenyang 110122,China
出 处:《Acta Pharmaceutica Sinica B》2022年第3期1432-1446,共15页药学学报(英文版)
基 金:funded by the National Natural Science Foundation of China(Nos.81773672 and 81903550)。
摘 要:In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws(CMSWs) with ideal topological structures(e.g., small section area, relative rough surface,screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bioadhesion, mucus-penetration and cellular uptake(contributed by the macropinocytosis and caveolaemediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres(CMSSs)and chiral mesoporous silica nanorods(CMSRs), achieving extended retention duration in the gastrointestinal(GI) tract and superior adsorption in the blood circulation(up to 2.61-and 5.65-times in AUC).After doxorubicin(DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier(IEB), and resulted in satisfactory oral bioavailability of DOX(up to 348%).CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.
关 键 词:Chiral mesoporous silica Nano-screw Morphology Geometric topological structure Intestinal epithelium barrier Oral adsorption
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