Polymeric drug delivery system
Author
Andersen, Camilla Lystlund
Term
4. term
Education
Publication year
2017
Submitted on
2017-02-03
Pages
100
Abstract
Dette kandidatprojekt undersøger brugen af polymermiceller baseret på polyvinylpyrrolidon (PVP) som transportsystem for lægemidler. Miceller er små kugler, som polymerer danner i vand; de kan gemme fedtskyende (hydrofobe) molekyler i deres indre. PVP med molekylvægt 1 og 6 kDa blev brugt til at danne miceller, enten med curcumin som model for et hydrofobt lægemiddel, eller som tomme miceller, midlertidigt stabiliseret med chloroform under fremstillingen. De fysiske egenskaber blev undersøgt med Nanoparticle Tracking Analysis for at måle størrelsesfordelingen og med Atomic Force Microscopy for at visualisere partiklerne. In vitro-forsøg blev udført på glioblastomaceller (U87) og fibroblaster (CRL 2429) for at undersøge cellers optagelse af micellerne og eventuel cellegiftighed (cytotoksicitet). Optisk fluorescensmikroskopi blev brugt til at følge, hvor meget curcumin cellerne optog i micelleform sammenlignet med fri curcumin. Cytotoksicitetsforsøg målte celledød efter 24 timers inkubation med forskellige koncentrationer af micellær og fri curcumin samt tomme miceller. For at belyse endocytose (cellernes optagelsesveje) blev der anvendt hæmmere som dynasore, wortmannin og natriumazid, efterfulgt af mikroskopi eller cytometriske målinger. Selvom optagelsesmekanismen ikke kunne fastslås endeligt, viste resultaterne, at curcumin i miceller optages langt bedre og virker mere effektivt end curcumin i fri form.
This Master’s project explores polyvinylpyrrolidone (PVP)-based polymer micelles as drug carriers. Micelles are tiny spheres formed by polymers in water that can hide oily (hydrophobic) molecules inside. PVP with molecular weights of 1 and 6 kDa was used to make micelles loaded with curcumin, a model hydrophobic compound, or empty micelles temporarily stabilized with chloroform during preparation. Physical properties were assessed by Nanoparticle Tracking Analysis to measure size distributions and Atomic Force Microscopy to visualize the particles. In vitro experiments on glioblastoma (U87) and fibroblast (CRL 2429) cell lines examined how cells take up micelles and potential cell toxicity (cytotoxicity). Optical fluorescence microscopy was used to compare cellular uptake of curcumin in micellar versus free form. Cytotoxicity assays measured cell death after 24 hours of exposure to varying concentrations of micellar curcumin, free curcumin, or empty micelles. To probe endocytosis pathways (how cells internalize materials), inhibitors such as dynasore, wortmannin, and sodium azide were applied, followed by microscopy or cytometry. Although the exact uptake mechanism could not be determined, the results show that micellar curcumin is taken up much more efficiently and is more effective than curcumin in its free form.
[This abstract was generated with the help of AI]
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