Surface charge tunable nanoparticles for TNF-(a) siRNA oral delivery for treating ulcerative colitis

Surface charge tunable nanoparticles for TNF-(a) siRNA oral delivery for treating ulcerative colitis

Shoaib Iqbal;Xiaojiao Du;Jilong Wang;Hongjun Li;Youyong Yuan;Jun Wang

【期刊名称】《纳米研究（英文版）》 【年(卷),期】2018(011)005

【摘要】Nanoparticle (NP) drug delivery systems have been successfully designed and implemented to orally deliver small interfering RNAs (siRNAs) for inflammatory disorders. However, the influence of surface charge on orally administered siRNA nanocarriers has not been investigated. In this study, we prepared structurally related poly(ethylene

glycol)-block-poly(lactic-co-glycolic

acid)

(PEG5k-b-

PLGA10k) NPs with the assistance of a synthesized lipid featuring surface amine groups for subsequent charge tuning. NPs were prepared by a double emulsion method, and their surface charge could be tuned and controlled by a succinylation reaction to yield NPs with different surface charges, while maintaining their size and composition. The prepared NPs were termed as aminated NPs (ANPs), plain NPs (PNPs), or carboxylated NPs (CNPs) based on their surface charge. All NPs exhibited the desired structural stability and siRNA integrity after enzymatic degradation. In vivo studies showed that ANPs significantly accumulated in inflamed colons, and they were successful in decreasing TNF-a secretion and mRNA expression levels while maintaining colonic

histology in a murine model of acute ulcerative colitis (UC). This study described a methodology to modify the surface charge of siRNA-encapsulating polymeric NPs and highlighted the influence of surface charge on oral delivery of siRNA for localized inflammatory disorders. 【总页数】13页(2872-2884) 【关键词】

【作者】Shoaib Iqbal;Xiaojiao Du;Jilong Wang;Hongjun Li;Youyong Yuan;Jun Wang

【作者单位】School of Life Sciences, University of Science and Technology of China, Hefei230027, China;School of Medicine, South China University of Technology, Guangzhou 510006, China;Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China;Key Laboratory of Biomedical Materials of Ministry of Education, South

China

University

of

Technology,

Guangzhou

510641,

China;National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China;School of Life Sciences, University of Science and Technology of China, Hefei230027, China;School of Medicine, South China University of Technology, Guangzhou 510006, China;Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China;School of Medicine, South

China

University

of

Technology,

Guangzhou

510006,

China;Institutes for Life Sciences, South China University of Technology,

Guangzhou 510006, China;National Engineering Research Center for Tissue

Restoration

and

Reconstruction,

Guangzhou

510006,

China;School of Medicine, South China University of Technology, Guangzhou 510006, China;Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China;Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, Guangzhou 510641, China;National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China;Research Institute for Food Nutrition and Human Health, Guangzhou 510641, China 【正文语种】英文 【中图分类】 【文献来源】

https://www.zhangqiaokeyan.com/academic-journal-cn_nano-research-english_thesis/0201243335684.html 【相关文献】

1.Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis [J], Shoaib Iqbal[1]; Xiaojiao Du[2,3,4,5]; Jilong Wang[1]; Hongjun Li[2,3]; Youyong Yuan[2,3,5]; Jun Wang[2,3,4,5,6]

2.TNF-αsiRNA表达载体的构建及其对胶原性关节炎大鼠TNF-α及IL-1的影响 [J], 庞春艳; 霍建新; 吕凤凤; 常志芳; 王永福