Cell-penetrating peptide enhanced insulin buccal absorption

You Xu, Xiaojuan Zhang, Nana Wang, Xing Pei, Yiyue Guo, Jianxin Wang, Stefan Barth, Fei Yu, Seung Jin Lee, Huining He, Victor C. Yang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Non-injectable delivery of peptides and proteins is not feasible due to the limitations of large molecular mass, high hydrophilic properties, and gastrointestinal degradation. Therefore, proposing a new method to solve this problem is a burning issue. The objective of this study was to propose a novel protein delivery strategy to overcome the poor efficacy and irritation of buccal insulin delivery. In this study, we applied a conjugate of cell-penetrating peptides (LMWP) and insulin (INS-PEG-LMWP) for buccal delivery. INS-PEG-LMWP was prepared using insulin solution and mixture as references. The transport behaviour, in vivo bioactivity, hypoglycaemic effect, and safety of INS-PEG-LMWP were systematically characterised. An in vitro study demonstrated that the uptake and transportation of INS-PEG-LMWP across buccal mucosal multilayers significantly increased. By comparing the effects of different endocytic inhibitors on INS-PEG-LMWP uptake, the conjugate might be delivered via an energy independent, electrostatically adsorbed pathway. INS-PEG-LMWP's relative pharmacological bioavailability was high and its relative bioavailability was up to 26.86%, demonstrating no visible mucosal irritation. Cell-penetrating peptides are likely to become a reliable and safe tool for overcoming insulin's low permeability through the epithelial multilayers, the major barrier to buccal delivery.

Original languageEnglish
Article number119469
JournalInternational Journal of Pharmaceutics
StatePublished - 30 Jun 2020

Bibliographical note

Funding Information:
We appreciate the financial support from the National Key Research and Development Plan (No. 2016YFE0119200 ) and the Young Elite Scientists Sponsorship Programme by Tianjin (No. TJSQNTJ-2017-14 ). This study was also supported in part by the National Natural Science Foundation of China (NSFC) (81361140344 A3 project).

Publisher Copyright:
© 2020 Elsevier B.V.


  • Buccal mucosal
  • Cell penetrating peptide
  • Hypoglycaemic effect
  • Insulin
  • Safety


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