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chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1432-1446页

作者： Yumei Wang Jia Ke Xianmou Guo Kaijun Gou Zhentao Sang Yanbu Wang Yan Bian Sanming Li Heran Li Department of Pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy China Medical UniversityShenyang 110122China

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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mesoporous silica nanoparticles with chiral pattern topological structure function as“antiskid tires”on the intestinal mucosa to facilitate oral drugs delivery

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Asian Journal of Pharmaceutical Sciences 2023年第2期18卷 106-123页

作者： Wei Xin Lin Wang Jiahui Lin Yanbu Wang Qi pan Yang Han Zhiye Bao Shun Zong Ying Cheng Xuchun Chen Lin Zhao Heran Li School of Pharmacy China Medical UniversityShenyang 110122China The First Hospital of China Medical University Shenyang 110001China

The weak adhesion between nanocarriers and the intestinal mucosa was one of the main reasons caused the failure in oral delivery.Inspired by the“antiskid tires”with complex chiral patterns,mesoporous silica nanoparticles AT-R@CMSN exhibiting geometrical chiral structure were designed to improve the surface/interface roughness in nanoscale,and employed as the hosting system for insoluble drugs nimesulide(NMS)and ibuprofen(IBU).Once performing the delivery tasks,AT-R@CMSN with rigid skeleton protected the loaded drug and reduced the irritation of drug on gastrointestinal tract(GIT),while their porous structure deprived drug crystal and improved drug release.More importantly,AT-R@CMSN functioned as“antiskid tire”to produce higher friction on intestinal mucosa and substantively influencedmultiple biological processes,including“contact”,“adhesion”,“retention”,“permeation”and“uptake”,compared to the achiral S@MSN,thereby improving the oral adsorption effectiveness of such drug delivery systems.By engineering AT-R@CMSN to overcome the stability,solubility and permeability bottlenecks of drugs,orally administered NMS or IBU loaded AT-R@CMSN could achieve higher relative bioavailability(705.95%and 444.42%,respectively)and stronger anti-inflammation effect.In addition,AT-R@CMSN displayed favorable biocompatibility and biodegradability.Undoubtedly,the present finding helped to understand the oral adsorption process of nanocarriers,and provided novel insights into the rational design of nanocarriers.

关键词： chiral mesoporous silica Bio-adhesion Oral delivery Intestinal mucosa Nanocarrier design

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