Cytotoxicity study of poly-N-vinyl-pyrrolidone-based polymeric drug delivery system

Cytotoksisk undersøgelse af poly-N-vinyl-2-pyrrolidone-baseret polymert medikamentleveringssystem

Rosenlund, Martin Brennodden

4. term

Nanotechnology, Master

2019

2019-10-22

117

Mange lægemidler har brug for små bærere for at nå det rigtige sted i kroppen. Dette speciale undersøger, om polymermiceller baseret på polyvinylpyrrolidon (PVP) er skadelige for celler. Miceller er nanoskala kugler, der kan transportere lægemidler. Selvom PVP-miceller tidligere er rapporteret som ikke-toksiske, fandt et tidligere speciale cellegiftighed, når micellerne blev fremstillet med en sonifikationsmetode (ultralyd). Derfor sammenlignede vi sonifikation med en co-solvent evaporation-metode (fordampning af et hjælpeopløsningsmiddel). Vi fremstillede miceller af PVP-OD med molekylvægte på 1, 3, 6 og 12 kDa ved 10x CMC (ti gange den koncentration, hvor miceller dannes). Med co-solvent evaporation så vi for 12 kDa en markant andel små aggregater på 10-100 nm sammenlignet med den anden metode og de øvrige polymerstørrelser. Vi testede cellegiftighed på fibroblaster (CRL 2429) og glioblastomceller (U87). For 6 kDa miceller fremstillet med sonifikation var der toksicitet over 0,08 mg/ml, uanset om micellerne var læssede eller tomme. For 12 kDa på fibroblaster var læssede miceller toksiske ved 0,1 mg/ml og tomme ved 0,08 mg/ml; på glioblastomceller var der kun toksicitet for læssede miceller ved 0,1 mg/ml. Resultaterne viste også, at det anvendte cytotoksicitetskit er mindre egnet til denne type polymere miceller. Samlet peger arbejdet på, at fremstillingsmetode, polymerstørrelse, læsning og celletype kan påvirke sikkerheden af PVP-miceller.

Many medicines rely on tiny carriers to reach the right place in the body. This thesis examines whether polyvinylpyrrolidone (PVP) polymer micelles are harmful to cells. Micelles are nanoscale spheres that can transport drugs. Although PVP micelles have been reported as non-toxic, a previous master’s project observed toxicity when micelles were prepared using a sonification method (ultrasonic treatment). We therefore compared sonification with a co-solvent evaporation method. Micelles from PVP-OD with molecular weights of 1, 3, 6 and 12 kDa were prepared at 10x CMC (ten times the concentration at which micelles form). With co-solvent evaporation, the 12 kDa polymer produced a notable fraction of small aggregates (10-100 nm) compared with the other method and polymer sizes. Cytotoxicity was tested on fibroblasts (CRL 2429) and glioblastoma cells (U87). For 6 kDa micelles made by sonification, toxicity appeared above 0.08 mg/ml whether the micelles were drug-loaded or empty. For 12 kDa micelles, on fibroblasts, loaded micelles were toxic at 0.1 mg/ml and empty micelles at 0.08 mg/ml; on glioblastoma cells, only loaded micelles were toxic at 0.1 mg/ml. The cytotoxicity assay kit used was also found to be sub-optimal for these polymeric micelles. Overall, the work indicates that preparation method, polymer size, loading and cell type can all influence the safety profile of PVP micelles.

[This abstract was generated with the help of AI]

cytotoksitet ; polymer ; miceller ; glioblastoma ; fibroblast ; pvp ; polyvinylpyrrolydine

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