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Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis

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Abstract

Nanoparticle (NP) drug delivery systems have been successfully designed and implemented to orally deliver 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-α 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.

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Acknowledgements

This work was supported by the National Basic Research Program of China (No. 2015CB932100), the National Natural Science Foundation of China (Nos. 51503195, 51390482 and 51633008), the National Key R&D Program of China (No. 2017YFA0205600), the Fundamental Research Funds for the Central Universities, and 111 Project (No. B17018). S.I. is also grateful for the CAS-TWAS president fellowship.

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Authors and Affiliations

  1. School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China

    Shoaib Iqbal & Jilong Wang

  2. School of Medicine, South China University of Technology, Guangzhou, 510006, China

    Xiaojiao Du, Hongjun Li, Youyong Yuan & Jun Wang

  3. Institutes for Life Sciences, South China University of Technology, Guangzhou, 510006, China

    Xiaojiao Du, Hongjun Li, Youyong Yuan & Jun Wang

  4. Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, Guangzhou, 510641, China

    Xiaojiao Du & Jun Wang

  5. National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou, 510006, China

    Xiaojiao Du, Youyong Yuan & Jun Wang

  6. Research Institute for Food Nutrition and Human Health, Guangzhou, 510641, China

    Jun Wang

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  1. Shoaib Iqbal
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  2. Xiaojiao Du
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Correspondence to Xiaojiao Du.

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Iqbal, S., Du, X., Wang, J. et al. Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis. Nano Res. 11, 2872–2884 (2018). https://doi.org/10.1007/s12274-017-1918-3

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  • DOI: https://doi.org/10.1007/s12274-017-1918-3

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