Cellular uptake and degradation behaviour of biodegradable poly(ethylene glycol-graft-methyl methacrylate) nanoparticles crosslinked with dimethacryloyl hydroxylamine
2011
Scheler, Stefan | Kitzan, Martina | Fahr, Alfred
Crosslinked polymers with hydrolytically cleavable linkages are highly interesting materials for the design of biodegradable drug carriers. The aim of this study was to investigate if nanoparticles made of such polymers have the potential to be used also for intracellular drug delivery. PEGylated nanoparticles were prepared by copolymerization of methacrylic acid esters and N,O-dimethacryloylhydroxylamine (DMHA). The particles were stable at pH 5.0. At pH 7.4 and 9.0 the degradation covered a time span of about 14 days, following first-order kinetics with higher crosslinked particles degrading slower. Cellular particle uptake and cytotoxicity were tested with L929 mouse fibroblasts. The particle uptake rate was found to correlate linearly with the surface charge and to increase as the zeta potential becomes less negative. Coating of the particle surface with polysorbate 80 drops the internalization rate close to zero and the charge dependence disappears. This indicates the existence of a second effect apart from surface charge. A similar pattern of correlation with zeta potential and coating was also found for the degree of membrane damage while there was no effect of polysorbate on the cell metabolism which increased as the negative charge decreased. It is discussed whether exocytotic processes may explain this behaviour.
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