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dc.contributor.advisorHamman, J H
dc.contributor.authorHaasbroek, Anja
dc.date.accessioned2018-06-11T09:27:32Z
dc.date.available2018-06-11T09:27:32Z
dc.date.issued2018
dc.identifier.urihttp://hdl.handle.net/10394/27383
dc.descriptionMSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2018en_US
dc.description.abstractOral drug delivery is one of the most preferred and user friendly routes of drug administration. Macromolecular drugs (such as peptides and proteins) generally have a poor bioavailability when administered orally. Absorption enhancers can be co-administered with macromolecular drugs to increase their bioavailability by either preventing enzymatic degradation or by increasing paracellular permeability (i.e. opening tight junctions). Various natural products have been investigated as possible absorption enhancers. Aloe vera ((L.) Burm.f.) leaf materials and N-trimethyl chitosan chloride (TMC) are examples of these natural products, which have shown the ability to increase the permeation of macromolecules across Caco-2 cell monolayers. In this study, the absorption enhancement abilities of A. vera gel and whole leaf extract were investigated by conducting in vitro transepithelial electrical resistance (TEER) and permeation studies across Caco-2 cell monolayers. For the TEER studies, Caco-2 cell monolayers were treated with different concentrations of A. vera gel and whole leaf extract solutions. The positive control used for the TEER study was 0.5% w/v N-trimethyl chitosan chloride (TMC; a known absorption enhancer) and the negative control used was media alone. The in vitro permeation of different molecular weight FITC-dextran molecules (i.e. 4 000 Da, 10 000 Da, 20 000 Da and 40 000 Da) was determined in the presence of different concentrations A. vera gel and whole leaf extract solutions to determine the capacity of absorption enhancement by the aloe leaf materials. In order to determine the mechanism of action of A. vera gel and whole leaf extract as drug absorption enhancers across intestinal epithelial cell monolayers, the Caco-2 cell monolayers were incubated with FITC-dextran to visualise the pathway of transport and F-actin was immunofluorescently stained to visualise if F-actin rearrangement occurred as a result of modulation by the aloe leaf materials. The application of A. vera gel and whole leaf extract solutions to Caco-2 cell monolayers resulted in a pronounced decrease in the TEER by all the concentrations of the aloe leaf materials tested in this study. The in vitro permeation of FITC-dextran 4 000 Da was markedly higher in the presence of A. vera gel and whole leaf extract (in all concentrations tested) compared to that of the control group. For the higher molecular weight FITC-dextran molecules (i.e. 10 000 Da, 20 000 Da and 40 000 Da), no absorption enhancement was seen with the addition of aloe leaf materials, indicating that these larger FITC-dextran molecules have exceeded the absorption enhancement abilities of the aloe leaf materials. With the confocal laser scanning microscopy (CLSM) study, the absorption enhancement of FITC-dextran via the paracellular pathway was confirmed as well as F-actin re-arrangement. The latter confirmed the involvement of tight junction modulation as the mechanism of absorption enhancement by A. vera gel and whole leaf extracten_US
dc.description.sponsorshipNational Research Foundation (NRF) North-West University (NWU)en_US
dc.language.isoenen_US
dc.publisherNorth-West University (South Africa), Potchefstroom Campusen_US
dc.subjectAbsorption enhancementen_US
dc.subjectAloe veraen_US
dc.subjectCaco-2en_US
dc.subjectCLSMen_US
dc.subjectF-actinen_US
dc.subjectFITC-dextranen_US
dc.subjectTEERen_US
dc.subjectTight junctionsen_US
dc.subjectParacellular permeabilityen_US
dc.titleDrug absorption enhancement capacities and mechanisms of action of Aloe vera gel materialsen_US
dc.typeThesisen_US
dc.description.thesistypeMastersen_US


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