A master thesis from Aalborg University
Cytotoxicity study of poly-N-vinyl-pyrrolidone-based polymeric drug delivery system
[Cytotoksisk undersøgelse af poly-N-vinyl-2-pyrrolidone-baseret polymert medikamentleveringssystem]
Author(s)
Term
4. term
Education
Publication year
2019
Submitted on
2019-10-22
Pages
117 pages
Abstract
Dette master-projekt fokuserer på cytotoksicitet af polyvinylpyrrolidon-baserede polymermiceller som et lægemiddelleveringssystem.Blandt de mange fokus på forberedelse til et lægemiddelafgivelsessystem er at kontrollere hver mulighed for krav, blandt disse er cytotoksicitet. Det er tidligere rapporteret at polyeret skal være ikke-giftigt. Imidlertid fandt et tidligere masterprojekt, at polymermicellerne dannet ved hjælp af en sonificeringsmetode var giftige. Dette blev undersøgt nærmere i denne afhandling, hvor sonificeringsmetode og co-opløsningsmiddeldampningsmetode blev anvendt til at skabe miceller fra 1 kDa, 3 kDa, 6 kDa og 12 kDa PVP-OD ved 10xCMC. Fremgangsmåde til fordampning med co-opløsningsmiddel viste en betydelig del af mindre aggregater 10-100 nm i 12 kDa i sammenligning med den anden fremgangsmåde og polymerstørrelser. Cytotoksisk assay blev udført på fibroblast (CRL 2429) og glioblastoma (U87), og det blev fundet, at sonificeringsmetoden for 6 kDa miceller var toksisk i koncentrationer over 0,08 mg /ml, uanset om den var indlæst eller tom. For 12 kDa var toksiciteten 0,1 mg/ml for indlæste miceller og 0,08 mg/ml for tomme miceller på fibroblastceller, mens de for glioblastomaceller kun var toksiske med indlæste miceller i koncentrationen på 0,1 mg / ml. Det er også vist, at det cytotoksiske assay-kit, der er anvendt i denne afhandling, er suboptimalt for disse polymere miceller.
This Master project focuses on the cytotoxicity of polyvinylpyrrolidone-based polymer micelles as a drug delivery system. Among the many focuses of preparation for a drug delivery system is checking each possibility of requirements, among these are cytotoxicity. It has previously been reported to be non-toxic. However, a previous master project found that the polymer micelles formed via a sonification method was toxic. This was investigated further in this thesis, where sonification method and co-solvent evaporation method was used to create micelles from 1 kDa,3 kDa, 6 kDa and 12 kDa PVP-OD at 10xCMC. The co-solvent evaporation method showed a significant portion of smaller aggregates 10-100 nm for 12 kDa, in comparison to the other method and polymer sizes. Cytotoxic assay was performed on fibroblast (CRL 2429) and glioblastoma (U87) and it was found that the sonification method for 6 kDa micelles was toxic at concentrations above 0.08 mg/ml regardless if it was loaded or empty. For 12 kDa, the toxicity was at 0.1 mg/ml for loaded micelles and 0.08 mg/ml for empty micelles on fibroblast cells, while for glioblastoma cells they were only toxic with loaded micelles at the concentration of 0.1 mg/ml. It was also shown that the cytotoxic assay kit used in this thesis is sub-optimal for these polymeric micelles.
Keywords
cytotoksitet ; polymer ; miceller ; glioblastoma ; fibroblast ; pvp ; polyvinylpyrrolydine
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