Bioinspired fine-tuning of the mechanical rigidity of SNEDDS for the efficient crossing of multiple gastrointestinal barriers

Jianbo Li; Yaru Xu; Jieke Zhang; Qinglian Li; Chenxu Wang; Zhe Wu; Weijing Yang; Meng Xu; Zhenzhong Zhang; Lei Wang; Jinjie Zhang

doi:10.1016/j.jconrel.2023.08.044

Bioinspired fine-tuning of the mechanical rigidity of SNEDDS for the efficient crossing of multiple gastrointestinal barriers

J Control Release. 2023 Oct:362:170-183. doi: 10.1016/j.jconrel.2023.08.044. Epub 2023 Aug 31.

Authors

Jianbo Li¹, Yaru Xu², Jieke Zhang², Qinglian Li², Chenxu Wang³, Zhe Wu², Weijing Yang², Meng Xu³, Zhenzhong Zhang⁴, Lei Wang⁵, Jinjie Zhang⁶

Affiliations

¹ Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, No.40. Daxue Road, Zhengzhou, Henan Province 450052, China.
² School of Pharmaceutical Sciences, Zhengzhou University, No.100. Kexue Road, Zhengzhou, Henan Province 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China.
³ Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, No.40. Daxue Road, Zhengzhou, Henan Province 450052, China; School of Basic Medical Sciences, Zhengzhou University, No.100. Kexue Road, Zhengzhou, Henan Province 450001, China.
⁴ School of Pharmaceutical Sciences, Zhengzhou University, No.100. Kexue Road, Zhengzhou, Henan Province 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China. Electronic address: zhangzhenzhong@zzu.edu.cn.
⁵ School of Pharmaceutical Sciences, Zhengzhou University, No.100. Kexue Road, Zhengzhou, Henan Province 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China. Electronic address: wanglei1@zzu.edu.cn.
⁶ School of Pharmaceutical Sciences, Zhengzhou University, No.100. Kexue Road, Zhengzhou, Henan Province 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China. Electronic address: ginger1029@zzu.edu.cn.

PMID: 37625600
DOI: 10.1016/j.jconrel.2023.08.044

Abstract

Nanoproperties, such as size, charge, and rigidity, have been demonstrated to be crucial for nanovehicles to overcome numerous gastrointestinal obstacles. However, the facile approach of modifying the rigidity of nanovehicles remains scarce, limiting understanding of how rigidity impacts their oral delivery. Inspired by the fact that cellular phospholipid content regulates plasma membrane rigidity, the rigidity of self-nanoemulsifiying drug delivery system (SNEDDS) could be fine-tuned via phosphocholine content while their size and zeta potential remain unchanged, using insulin as a model drug. Notably, soft SNEDDS exerted longer gastrointestinal transit time, higher drug release rate, stronger gastrointestinal stability and relatively lower mucus permeation but superior epithelial transcytosis than their hard counterparts in a macropinocytosis-dependent manner. The rigidity-related enhanced transcytosis was attributed to improved endocytosis, lysosome escape capability and exocytosis. Rats with type 1 diabetes exhibited greater oral insulin absorption and blood glucose lowering effect with soft SNEDDS. This study demonstrated the regulatory role of phospholipids in nanovehicle rigidity, which could help develop mechanically optimized nanomedicines in the future.

Keywords: Epithelium; Mucus; Oral delivery; Phospholipids; Rigidity.