Polymeric micelles as drug delivery system and MRI contrast agent
Translated title
Polymeriske miceller som drug delivery system og MRI contrast stof
Author
Term
4. term
Education
Publication year
2015
Submitted on
2015-09-16
Pages
91
Abstract
Afhandlingen udforskede den potentielle anvendelse af amphifile PVP miceller som laegemiddeladministrationssystem og gadolinium MRI-kontrastmiddel. PVP miceller blev fremstillet i 30 til 100 nm stoerrelsesorden, og deres evne til laegemiddelafgivelse blev undersoegt. Glioblastoma og fibroblastceller blev udsat for curcumin fyldte PVP miceller under tilstedevaerelse af endocytiske inhibitorer, dynasore og wortmannin, og optagelse af laegemiddel blev observeret efter mindre end 5 minutters eksponering påå tvaers af alle eksperimentelle linjer. Curcumin fyldte PVP miceller blev funktionaliseret med gadolinium for at fungere som kontrastmiddel til in vivo MR-scanning af noegne mus. Et intravaskulaer T1 vaegtet signal blev observeret, som var omkring halv saa stort som en kommerciel standard Dotarem som reference. "Enhanced permeability and retention time" (EPR) effekten blev observeret i tumoren i musen underlagt proeven af staerkeste signal intensitet, i form af akkumuleret signal efter 24 timer.
The thesis explored the potential application of amphiphilic PVP micelles as drug delivery system and gadolinium MRI contrast agent. PVP micelles were produced in 30 to 100 nm size range, and their drug delivery ability was investigated. Glioblastoma and fibroblast cells were exposed to curcumin loaded PVP micelles in the presence of endocytic inhibitors, dynasore and wortmannin, and drug uptake was observed within 5 minutes of exposure across all experimental lines. The curcumin loaded PVP micelles were functionalised by gadolinium to serve as a contrast agent for \textit{in vivo} MRI scan of nude mice. An intravascular T1 weighted signal was observed, of about half the magnitude compared to commercial agent Dotarem as reference. The enhanced permeability and retention time (EPR) effect was observed in the tumour of the mouse subject to sample of strongest signal intensity, by the accumulated signal after 24 hours.
Keywords
Polymeric ; Drug delivery systems ; Micelles ; MRI contrast agent ; Gd-DTPA ; PVP ; Curcumin ; Microscopy ; NTA ; Peptide synthesis ; In vivo ; In vitro ; EPR effect ; HPLC
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