Aufnahmemechanismus und Wirkung chemotherapeutisch beladener Miniemulsions-Nanopartikel in Tumorzellen
FacultiesFakultät für Naturwissenschaften
LicenseStandard (Fassung vom 01.10.2008)
The interaction of polymeric nanoparticles (NP) with cells was characterized by flow cytometry, confocal fluorescence and electron microscopy. Extensive studies with different, in detail characterized NP showed in direct comparison that the stabilization and functionalization of 100-250 nm-sized NP but also the polymer type influences the NP uptake. Biodegradable NP consisting of poly(L-lactide) (PLLA), poly(epsilon-caprolactone) and poly(D,L-lactide-co-glycolide) with non-ionic or anionic stabilization were studied in HeLa and Jurkat cells. Uptake kinetics of differently stabilized polystyrene (PS) and PLLA NP show that the influence of the surface charge exceeds that of the polymer type. An outstanding uptake augmenting effect of approx. factor 5 is caused by amino functionalization. In studies with ten different inhibitory drugs, it was shown that the involved endocytotic mechanisms are dependent on the system of NP and the cells. Lipid raft-dependent endocytosis was shown in all systems studied and was often dynamin-dependent. Macropinocytosis was also shown in many systems but clathrin-dependent endocytosis was only detected with aminofunctionalized NP. A further subproject was establishing a blood brain barrier (BBB) model to check different NP formulations for their ability to pass the BBB. Human brain microvascular endothelial cells were chosen as model cells in a transwell system. Poly(butylcyanoacrylate) NP were tested as potential drug carriers and the results were compared with analogous in vivo studies. As drug transport is also interesting with regard to tumors beyond the brain, the effect of NP-associated paclitaxel on HeLa and MCF-7 cells was studied. Paclitaxel-containing PS or PLLA NP were effective in HeLa and MCF-7 cells. This thesis shows that the interaction of NP and cells is dependent on many factors, so there is much potential to optimize NP for different applications.
Subject HeadingsMiniemulsion [GND]
Blood brain barrier [MeSH]
Drug delivery systems [MeSH]