2016
DOI: 10.1038/srep32498
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Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers

Abstract: 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) wit… Show more

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Cited by 30 publications
(18 citation statements)
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“…In this context, the isoelectric point of insulin is 5.6; under acidic conditions, the acidic groups on insulin become protonated, and the basic amino groups provide the resulting charge . Carboxyl groups of glutamic acid also have the capacity for ionization, so under the pH conditions of the experiment, both the glutamic acid and insulin may be ionized and able to form stable ion pairs and soluble complexes as has been suggested before . In the third stage of the experiment, the solutions analyzed were adjusted to pH 1.2 to simulate gastric pH condition.…”
Section: Resultsmentioning
confidence: 99%
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“…In this context, the isoelectric point of insulin is 5.6; under acidic conditions, the acidic groups on insulin become protonated, and the basic amino groups provide the resulting charge . Carboxyl groups of glutamic acid also have the capacity for ionization, so under the pH conditions of the experiment, both the glutamic acid and insulin may be ionized and able to form stable ion pairs and soluble complexes as has been suggested before . In the third stage of the experiment, the solutions analyzed were adjusted to pH 1.2 to simulate gastric pH condition.…”
Section: Resultsmentioning
confidence: 99%
“…A previous patent has proposed the use of glutamic acid to reduce the insulin aggregation, and results from Quinn and Andrade have confirmed this observation. These authors propose that the effect is due to an ion‐pairing mechanism that causes interference with insulin–insulin interactions and found that the anti‐aggregation effect is pH‐dependent . Besides, glutamic acid has been reported to act as a permeation enhancer for insulin in buccal cell layers by the ion‐pairing mechanism mentioned above …”
Section: Introductionmentioning
confidence: 99%
“…The permeability studies were performed as described by Iyire et al with a slight modification (Figure 1). 3 The studies were done across TR146 cell layers from apical (0.5 mL) to basolateral direction (1. ), and enhancement ratio (ER) were calculated from the linear part of the permeation curve as described by Oh et al 5 J s was obtained from Equation 6, where Q r is the total permeated insulin (ng), A is the cross-sectional diffusion area (cm 2 ), and t is the time of exposure (hour).…”
Section: In Vitro Cell Permeation Studiesmentioning
confidence: 99%
“…Thus, these findings reveal that some amount of insulin was permeated through the transcellular route. 3…”
Section: Interaction Of Various Elastic Bilosomes With Tr146 Cellsmentioning
confidence: 99%
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