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    Combining chemical permeation enhancers to obtain synergistic effects

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    Date
    2014
    Author
    Du Toit, Trizel
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    Abstract
    The oral route of administration remains the preferred route of administrating drugs due to patient acceptance and compliance. Therapeutic proteins are currently mainly administered by means of the parenteral route because of its low intestinal epithelial permeation capability. The major challenges for oral delivery of proteins and peptides are pre-systemic enzymatic degradation and poor penetration of the intestinal mucosa. The latter can be overcome by including safe and effective absorption enhancers in dosage forms. Aloe vera, Aloe ferox and Aloe marlothii gel materials as well as N-trimethyl chitosan chloride (TMC) were shown to be capable of increasing peptide drug transport across in vitro models such as Caco-2 cell monolayers. The purpose of this study is to investigate binary combinations of chemical drug absorption enhancers and to determine if synergistic drug absorption enhancement effects exist. A. vera, A. ferox and A. 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 single components.
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    http://hdl.handle.net/10394/15206
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