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Research Article

Single small molecule-assembled nanoparticles mediate efficient oral drug delivery

Xin Yang1,3<, Chao Ma2,3<, Zeming Chen3, Jun Liu3, Fuyao Liu3, Rongbin Xie4, Haitian Zhao1,3, Gang Deng3, Ann T. Chen5, Ningbo Gong6, Lei Yao1,3, Pengjian Zuo1, Kangkang Zhi1, Jiacheng Wang1, Xiaobin Gao7, Jing Wang1, Louzhen Fan4, Jiangbing Zhou3,5( )
School of Chemistry and Chemical Engineering,Harbin Institute of Technology,Harbin,150090,China;
College of Biological Sciences and Biotechnology,Beijing Forestry University,Beijing,100083,China;
Department of Neurosurgery,Yale University,New Haven, CT,06510,USA;
Department of Chemistry,Beijing Normal University,Beijing,100875,China;
Department of Biomedical Engineering,Yale University,New Haven, CT,06510,USA;
Beijing Key Laboratory of Polymorphic Drugs,Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100050,China;
Department of Pathology,Yale University,New Haven, CT,06510,USA;

§ Xin Yang and Chao Ma contributed equally to this work.

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Graphical Abstract

Abstract

Oral drug delivery, which requires surviving the harsh environment in the gastrointestinal (GI) tract and penetrating the intestinal epithelium, has not been achieved using simple formulation nanoparticles (NPs). Medicinal natural products (MNPs) have been widely used in traditional medicine for disease management through oral consumption. However, most pharmacologically active compounds within MNPs do not have the properties suitable for oral applications. We hypothesize that some MNPs contain natural nanomaterials that can convert those compounds into oral formulations by forming NPs. After screening 66 MNPs, we identified five classes of small molecules that form NPs, many of which are capable of efficient drug encapsulation and GI penetration. We show that one of them, dehydrotrametenolic acid (DTA), is capable of mediating oral delivery for effective disease treatment. We determined that DTA NPs assemble through hydrogen bonding and penetrate the GI tract via apical sodium-dependent bile acid transporter. Our study reveals a novel class of single component, small molecule-assembled NPs for oral drug delivery, and suggests a novel approach to modernizing MNPs through nanomaterial discovery.

Keywords

natural materialoral drug deliverynanoparticledehydrotrametenolic acid (DTA)

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Nano Research
Volume 12 Issue 10,
October 2019
Pages 2468-2476
DOI: 10.1007/s12274-019-2470-0
Cite this article:
Yang X, Ma C, Chen Z, et al. Single small molecule-assembled nanoparticles mediate efficient oral drug delivery. Nano Research, 2019, 12(10): 2468-2476. https://doi.org/10.1007/s12274-019-2470-0
Topics:
DiagnosisDiseasesHydrogen bonds NanoparticlesNanostructured materialsTargeted drug delivery

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Received: 11 December 2018
Revised: 01 July 2019
Accepted: 01 July 2019
Published: 24 July 2019
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019
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