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Membrane fusion reverse micelle platforms as potential oral nanocarriers for efficient internalization of free hydrophilic peptides

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An Erratum to this article was published on 26 June 2023

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Abstract

Orally administered peptides or proteins are garnering increasing preference owing to their superiority in terms of patient compliance and convenience. However, the development of oral protein formulations has stalled due to the low bioavailability of macromolecules that encounter the aggressive gastrointestinal environment and harsh mucus villi barrier. Herein, we propose an ideal reverse micelle/self-emulsifying drug delivery system (RM/SEDDS) nanoplatform that is capable of improving the oral bioavailability of hydrophilic peptides by preventing enzymatic degradation and enhancing mucosal permeability. Upon the passage through the mucus, the self-emulsifying drug delivery system with optimal surface properties effectively penetrates the viscoelastic mucosal barrier, followed by the exposure of the inner reverse micelle amphipathic vectors, which autonomously form continua with the lipidic cell membrane and facilitate the internalization of drugs. This membrane-fusion mechanism inaugurates a new way for hydrophilic peptide delivery in the free form, circumventing the traditional impediments of the cellular internalization of nanocarriers and subsequent poor release of drugs. And more importantly, reverse micelles are not spatially specific to the laden drugs, which enables their delivery for a myriad of peptide clinical drugs. In conclusion, as an exquisitely designed nanoplatform, RM/SEDDS overcomes multiple physiological barriers and opens a new path for drug cellular entry, providing new prospects for the development of oral drug delivery systems.

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Acknowledgments

This work was supported by the National Key Research and Development Program of China (No. 2022YFE0107800) and National Natural Science Foundation of China (Nos. 82073332, and 81673022). We thank Mengjie Yu at Bio-Ultrastructure Analysis Lab. of Analysis Center of Agrobiology and Environmental Sciences, Zhejiang University for her technical assistance on transmission electron microscopy; Qin Han, Chenyu Yang, Juanli Xuan, and Dandan Song at the Center of Cryo-Electron Microscopy (CCEM), Zhejiang University for their technical assistance on confocal laser scanning microscopy and transmission electron microscopy.

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  1. Mengting Lin, Linjie Wu, and Yiying Lu contributed equally to this work.

Authors and Affiliations

  1. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    Mengting Lin, Linjie Wu, Yiying Lu, Xiaoyan Bao, Haiqing Zhong, Qi Dai, Qiyao Yang, Yiyi Xia, Xin Tan, Yaxin Qin, Ruolin Jiang & Min Han

  2. Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou, 310058, China

    Min Han

  3. The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310058, China

    Qi Dai, Qiyao Yang & Min Han

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  1. Mengting Lin
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Correspondence to Min Han.

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Membrane fusion reverse micelle platforms as potential oral nanocarriers for efficient internalization of free hydrophilic peptides

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Lin, M., Wu, L., Lu, Y. et al. Membrane fusion reverse micelle platforms as potential oral nanocarriers for efficient internalization of free hydrophilic peptides. Nano Res. 16, 9768–9780 (2023). https://doi.org/10.1007/s12274-023-5645-7

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