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Combining Chemical Permeation Enhancers for Synergistic Effects

Abstract

Currently, macromolecular drugs such as proteins are mainly administered by means of injections due to their low intestinal epithelial permeability and poor stability in the gastrointestinal tract. This study investigated binary combinations of chemical drug absorption enhancers to determine if synergistic drug absorption enhancement effects exist. Aloe vera, Aloe ferox and Aloe marlothii leaf gel materials, as well as with N-trimethyl chitosan chloride (TMC), were combined in different ratios and their effects on the transepithelial electrical resistance (TEER), as well as the transport of FITC-dextran across Caco-2 cell monolayers, were measured. The isobole method was applied to determine the type of interaction that exists between the absorption enhancers combinations. The TEER results showed synergism existed for the combinations between A. vera and A. marlothii, A. marlothii and A. ferox as well as A. vera and TMC. Antagonism interactions also occurred and can probably be explained by chemical reactions between the chemical permeation enhancers, such as complex formation. In terms of FITC-dextran transport, synergism was found for combinations between A. vera and A. marlothii, A. marlothii and A. ferox, A. vera and TMC, A. ferox and TMC and A. marlothii and TMC, whereas antagonism was observed for A. vera and A. ferox. The combinations where synergism was obtained have the potential to be used as effective drug absorption enhancers at lower concentrations compared to the single components.

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Acknowledgments

This work was carried out with the financial support of the National Research Foundation of South Africa. Any opinion, findings and conclusions or recommendations expressed in this material are those of the authors and therefore the NRF do not accept any liability with regard thereto.

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The authors report no conflict of interest.

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Correspondence to Josias H. Hamman.

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du Toit, T., Malan, M.M., Lemmer, H.J.R. et al. Combining Chemical Permeation Enhancers for Synergistic Effects. Eur J Drug Metab Pharmacokinet 41, 575–586 (2016). https://doi.org/10.1007/s13318-015-0280-7

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  • DOI: https://doi.org/10.1007/s13318-015-0280-7

Keywords

  • Negative Control Group
  • Permeation Enhancer
  • Absorption Enhancer
  • Iodomethane
  • Basolateral Chamber