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Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers
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Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers
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Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers
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Journal Article
Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers
2016
Overview
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 are 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
