Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers

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The aim of this work was to investigate alternative safe and effective permeation enhancers for buccal peptide delivery. Basic amino acids improved insulin solubility in water while 200 and 400 µg/mL lysine significantly increased insulin solubility in HBSS. Permeability data showed a significant improvement in insulin permeation especially for 10 µg/mL of lysine (p < 0.05) and 10 µg/mL histidine (p < 0.001), 100 µg/mL of glutamic acid (p < 0.05) and 200 µg/mL of glutamic acid and aspartic acid (p < 0.001) without affecting cell integrity; in contrast to sodium deoxycholate which enhanced insulin permeability but was toxic to the cells. It was hypothesized that both amino acids and insulin were ionised at buccal cavity pH and able to form stable ion pairs which penetrated the cells as one entity; while possibly triggering amino acid nutrient transporters on cell surfaces. Evidence of these transport mechanisms was seen with reduction of insulin transport at suboptimal temperatures as well as with basal-to-apical vectoral transport, and confocal imaging of transcellular insulin transport. These results obtained for insulin is the first indication of a possible amino acid mediated transport of insulin via formation of insulin-amino acid neutral complexes by the ion pairing mechanism.

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  • Amino acid assisted permeability of insulin

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Original languageEnglish
Article number32498
Number of pages27
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 1 Sep 2016

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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ Iyire, A., Alaayedi, M., & Mohammed, A. R. (2016). Corrigendum: Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers. Scientific Reports, 6, 34883. DOI: 10.1038/srep34883 Supplementary information accompanies this paper at http://www.nature.com/srep

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