Mastergradsoppgaver i farmasi
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Mastergradsoppgaver i farmasi
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Berg, Ole Aleksander (Master thesis; Mastergradsoppgave, 20-May-2011)[+][-]
Abstract: Trauma to the skin in the form of severe wound, particularly burns, can facilitate colonization of potentially life threatening bacterial infections. To prevent infections of the wounded area, antimicrobial agents are recommended as standard treatment. Topical administration of antimicrobial agents, such as mupirocin, can provide local therapy, while avoiding the risks of systemic administration. Mupirocin-in-liposomes-in hydrogels were proposed as advanced delivery system for this purpose. Up to now, no liposomal mupirocin for topical administration has been reported. Chitosan was selected as hydrogel matrix due to its biodegradability and in-built antimicrobial and wound healing potentials. Phosphatidylcholine liposomes containing mupirocin, namely non-sonicated and sonicated liposomes, were characterized for vesicle size and size distributions. Non-sonicated vesicles entrapped in average 74 and sonicated 49 % of mupirocin calcium, respectively. Sonication reduced the original vesicle size from around 1 micron down to 135 nm. Liposomes (10 %, w/w) were incorporated in chitosan hydrogels and liposomal hydrogels evaluated for their textural properties. Hydrogels were found to exhibit satisfactory adhesiveness and cohesiveness, with corresponding stability profile. Microbiological assessment confirmed antibacterial properties of liposomally entrapped mupirocin incorporated in hydrogels. In vitro and ex vivo (on pig skin) drug release profiles of various formulations containing mupirocin were performed on Franz diffusion cells. Liposomal hydrogels were compared with marketed mupirocin product, Bactroban® cream. The release studies showed that liposomal size affects the release of the incorporated drug. Liposomal hydrogels were shown to provide sustained release of incorporated mupirocin. In conclusion, liposomal hydrogels developed for mupirocin offer the potential to increase retention time and provide sustained release of a drug, which are important parameters for improved treatment of wounds, including burns. URI: http://hdl.handle.net/10037/3689 File(s) in this item: 1
thesis.pdf (71.30Mb) -
Andersen, Toril (Master thesis; Mastergradsoppgave, 16-Jun-2010)[+][-]
Abstract: Calanus finmarchicus is a vast resource that until recently have been exploited to a minimal degree only. In the last few years harvesting and processing methods have been developed. There is a large market and great interest in products derived from marine oils. Most of the products today are derived from organisms at a high trophic level, i.e. products derived from cod liver oil. One disadvantage with these products is high levels of fat-soluble pollutants that require extensive purification before the products can be released to the market. As C. finmarchicus exists on the first trophic levels it is not polluted and is therefore very interesting as a substitution for cod liver oil, which is the main source for ω-3 fatty acids. In addition to this studies have shown that the oil extracted from the animal, Calanus oil, have beneficial properties and can reduce the risk for coronary heart disease, cancer and inflammation and this could be attributed to the contents of wax esters, high levels of a natural antioxidant, Astaxantine, and high levels of phytosterols. The aim of this thesis was to isolate and characterize the wax esters of the oil, and elucidate their structure. The wax esters were first separated from the Calanus oil with silica SPE and then transesterified to FAME and FAL. The two structures types were separated into two fractions with APS SPE. The FAME were analyzed as their picolinyl esters in GC-MS for structure elucidation and the FAL as their nicotinate esters and TMS ethers. The fractions from various SPE columns were tested by use of TLC and/or GC-MS to confirm that they contained the actual compounds. The FAME found were in a range of 14 to 22 carbon chain length, and there were saturated, monounsaturated and polyunsaturated FAME present. The PUFA were 18:4 (n-5, 7, 9, 11) and 22:5 (n-5, 7, 9, 11, 13). The FAL identified ranged from 16 to 22 carbon atoms in chain length, and were mostly monounsaturated, but one saturated compound was found. The next step would now be to analyze the wax esters in LC-MS to find the complete structure using the pieces of structure found in the FAME and FAL, as there are limited numbers of combinations of the FAME and FAL in a wax ester. URI: http://hdl.handle.net/10037/3526 File(s) in this item: 1
thesis.pdf (6.882Mb) -
Køller, Katrine Sperstad (Master thesis; Mastergradsoppgave, 16-Jun-2011)[+][-]
Abstract: Conotoxins are small disulfide rich peptides derived from the venom of Cone snails. They target different receptors in the nervous system with high selectivity and potency making them valuable as drug leads or drug themselves. One group of conotoxins, α-conotoxins have been shown to have potential as treatment for neuropathic pain. URI: http://hdl.handle.net/10037/3429 File(s) in this item: 1
thesis.pdf (2.180Mb) -
Elvheim, Iselin Sørstad (Master thesis; Mastergradsoppgave, Jun-2011)[+][-]
Abstract: The relaxin family of peptides consists of seven structurally related peptides, with a wide variety of biological functions, ranging from involvement in reproductive processes to functions as neuroendocrine modulators. Because of the complex, two-chained structure of the relaxins, and their lack of specificity for the various relaxin family receptors (RXFPs), design of simpler, more selective analogues is important for further investigation of their biological functions and as potential drug leads. The aim of this project was to introduce a helical structure around the receptor-binding region of single-chain relaxin analogues. This was approached by utilising helix capping sequences on truncated relaxin B-chains and by grafting of residues important for binding onto a stable peptide scaffold. Helix capping enhanced the helical properties compared to previous single- chain analogues, but was unable to introduce a sufficiently stable helix. Despite the increased helical tendencies, no high-affinity analogues were found. As a result, the importance of Arg8 was investigated, and we have demonstrated that this residue might be more involved in binding than previously thought. We successfully synthesised a relaxin-3/chlorotoxin analogue, which appeared to fold correctly. However, the yield following oxidation was poor, and no bioactivity data or structural data confirming the correct fold was obtained within the time limits of the project. A secondary aim was to probe for favourable mutations around the receptor- binding region by synthesising a combinational library. We were able to successfully synthesise a library of peptides with mutations in one position by inserting a mixture of amino acids at this coupling step in the solid phase peptide synthesis (SPPS) procedure. Although no significant improvement in binding was seen for the analogues generated, important methodological advances were made that will be used to scan different positions for new contact points with the receptor. URI: http://hdl.handle.net/10037/3428 File(s) in this item: 1
thesis.pdf (11.68Mb) -
Mobasheri, Mina (Master thesis; Mastergradsoppgave, 06-Jun-2011)[+][-]
Abstract: Pax6 og Pax6(5a) er to isoformer av den evolusjonært konserverte transkripsjonsfaktoren som blir uttrykt i blant annet hjernen, øyne, nese og pankreas hos virveldyr under embryoutvikling. Uttrykket av Pax6 vil vedvare hos voksne individer, blant annet i øyne, hjernen og pankreas. Den er viktig for vedlikehold av stamceller, men har også en stor betydning for celle differensiering i mange vev. Aniridia hos mennesker og small eye i mus er blant de sykdommene som forekommer pga. mutasjoner i ett Pax6-gen. Dersom det forekommer mutasjoner i begge Pax6 genene vil fosteret ved fødsel ikke ha øyne, deler av hjernen vil være manglende eller underutviklet og nasale strukturer vil også mangle. Derfor dør fosteret kort tid etter fødsel. Pax6 er også forbundet med kreftformer slik som glioblastoma. De to isoformene (Pax6 og Pax6(5a)) har forskjellige DNA bindings egenskaper, men blir uttrykt i de fleste celletyper samtidig, slik som i øyne. For å få en oversikt over hvilke målgener de to isoformene regulerer, ble det i forkant av dette prosjektet brukt genekspresjons microarray og en del av resultatene ble bekreftet ved hjelp av qPCR metoder. Det ble oppdaget et lite, men signifikant antall gener som ble regulert av Pax6 og/eller Pax6 i stabil transfekterte 3T3 fibroblaster. Noen av disse er felles målgen for begge isoformene. Men disse blir regulert i forskjellig grad av Pax6 og Pax6(5a). Et målgen som viste seg å bli regulert av både Pax6 og Pax6(5a) var Dickopf3(DKK3). DKK3 er et medlem av Dickkopf (DKK) familien som er antagonister av Wnt – signalveien. I disse undersøkelsene viste det seg at DKK3 er 18 fold oppregulert av Pax6(5a) i 3T3-fibroblaster fra mus, og 3 fold oppregulert av Pax6. Mulige målseter for Pax6 og Pax6(5a) i promoteren til både mus og menneske DKK3 genet har også blitt identifisert ved bruk av bioinformatikk. I denne oppgaven ble DKK3 promoteren fra mus og menneske klonet og ko–transfektert sammen med plasmider som kodet for Pax6 og Pax6(5a). Vi kunne tydelig se at mDKK3 promoteren ble positivt påvirket ved reporter gen assay analyser. Det ble også jort forsøk på å klone sebrafisk cDNA’ et som koder for DKK3, med tanke på å lage en probe for sebrafisk in situ hybridiseringer. Videre ble det utført transient transfeksjon av plasmider som koder for Pax6 og Pax6(5a) inn i 3T3-kontroll cellene for å se om korttids – uttrykket av Pax6 og Pax6(5a) gir samme resultat som de stabilt transfekterte cellelinjene med tanke på DKK3’ gen uttrykket. Protein uttrykket av Pax6 og Pax6(5a) ble bekreftet, men endringer i DKK3 RNA uttrykk kunne ikke identifiseres ved bruk av qPCR. URI: http://hdl.handle.net/10037/3424 File(s) in this item: 1
thesis.pdf (2.540Mb)
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