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dc.contributor.advisorBrandl, Martin
dc.contributor.advisorMassing, Ulrich
dc.contributor.authorMøkleby, Tormund Aasjord
dc.date.accessioned2009-10-21T07:42:39Z
dc.date.available2009-10-21T07:42:39Z
dc.date.issued2009-05
dc.description.abstractGemcitabine is a well established anticancer compound, and is in use today against several types of cancers. Gemcitabine has a short half life. Formulations of gemcitabine containing liposomes could extend it's half life, thereby maybe improving its effectiveness. Also, liposomes in the smaller size range have an advantage when it comes to treating cancer. They accumulate at the site of the tumor, and stay there for a longer time than it would have done in normal tissue(Massing and Fuxius 2000). Previous attempts to actively load gemcitabine into liposomes have used a pH gradient with acidic pH inside compared to more neutral pH on the outside of the liposomes, accomplished by an ammonium sulphate gradient. But this approach showed some difficulties; among other things that gemcitabine had a tendency to leak out in very short time. (Gravem 2006). In this thesis I have among other things investigated the possibility of loading gemcitabine into liposomes by precipitation. The hope was that this could give higher trapping efficiency and reduced leakage compared to the ammonium sulphate approach. Firstly, for comparable reasons and method development, an approach to load liposomes via an ammonium sulphate gradient was tried. Thought after encountering several problems the experiment was ended without any results indicating loading, most likely due to heavily diluted liposomes. Secondly I investigated if I could make gemcitabine precipitate. Firstly I tried a great range of different phosphate and sulphate salts, to test if any of them would cause a precipitation. Precipitation seemed to be independent of which salt used, but enhanced by factors such as high concentration of gemcitabine, alkaline conditions (pH ≥ 6), and low temperature. The two last conditions were the total opposites of loading via an ammonium sulphate gradient, and contained several contradictions as it meant that the outer pH had to be significantly lower to avoid precipitation and that a low temperature made it harder for gemcitabine to cross the membrane of the liposomes. An attempt to load gemcitabine into liposomes, using a pH 4 in the outer phase and pH 7 in the inner phase of the liposomes, with repeated cooling and freezing cycles, revealed poor loading. Thought optimizing conditions such as pHs, and time and temperatures in the cooling freezing cycles might enhance the loading a bit it is difficult to see this approach becoming a success.en
dc.format.extent1114690 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10037/2202
dc.identifier.urnURN:NBN:no-uit_munin_1954
dc.language.isoengen
dc.publisherUniversitetet i Tromsøen
dc.publisherUniversity of Tromsøen
dc.rights.accessRightsopenAccess
dc.rights.holderCopyright 2009 The Author(s)
dc.subject.courseIDFAR-3901nor
dc.subjectVDP::Technology: 500::Medical technology: 620en
dc.subjectsolubilityen
dc.subjectactive loadingen
dc.subjectgemcitabineen
dc.subjectliposomesen
dc.subjectloadingen
dc.subjectprecipitationen
dc.titleActive loading of gemcitabine into liposomesen
dc.typeMaster thesisen
dc.typeMastergradsoppgaveen


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