Combining Chemical Permeation Enhancers for Synergistic Effects.
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.
Faculty of Health Sciences, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Trizel
T
du Toit
Faculty of Health Sciences, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Maides M
MM
Malan
Faculty of Health Sciences, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Hendrik J R
HJ
Lemmer
Faculty of Health Sciences, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Chrisna
C
Gouws
Faculty of Health Sciences, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Marique E
ME
Aucamp
Statistical Consultation Services, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Wilma J
WJ
Breytenbach
Faculty of Health Sciences, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa. sias.hamman@nwu.ac.za.
Josias H
http://orcid.org/0000-0002-8916-3927
JH
Hamman
D000504:Aloe / Q000737:chemistry; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004357:Drug Synergism; D017097:Electric Impedance; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D010539:Permeability; D010936:Plant Extracts / Q000008:administration & dosage / Q000378:metabolism*; D018515:Plant Leaves / Q000737:chemistry
D003911:Dextrans; D004337:Drug Carriers; C118071:N-trimethyl chitosan chloride; D010936:Plant Extracts; C015219:fluorescein isothiocyanate dextran; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate