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Research Article

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

Mengting Lin1,§, Linjie Wu1,§, Yiying Lu1,2,§, Xiaoyan Bao1, Haiqing Zhong1, Qi Dai1,4, Qiyao Yang1,4, Yiyi Xia1, Xin Tan1, Yaxin Qin1, Ruolin Jiang1, Min Han1,3,4 ( )
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, China
The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310058, China

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

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An erratum to this article is available online at:
https://doi.org/10.1007/s12274-023-5925-2

Graphical Abstract

Schematic illustration of reverse micelle/self-emulsifying drug delivery system (RM/SEDDS) gastrointestinal transport, mucus penetration and membrane fusion processes to facilitate the internalization of free hydrophilic peptides.

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.

Keywords

oral drug delivery systemreverse micelleself-emulsifying drug delivery systemmembrane fusionhydrophilic peptide

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Nano Research
Volume 16 Issue 7,
July 2023
Pages 9768-9780
DOI: 10.1007/s12274-023-5645-7
Cite this article:
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 Research, 2023, 16(7): 9768-9780. https://doi.org/10.1007/s12274-023-5645-7
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Drug delivery

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Received: 04 December 2022
Revised: 27 February 2023
Accepted: 07 March 2023
Published: 14 April 2023
© Tsinghua University Press, corrected publication 2023
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