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Polymeric nanoparticles of different sizes overcome the cell membrane barrier

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V | 21 Feb 2013

S Lerch, M Dass, A Musyanovych, K Landfester and V Mailänder
Abstract
Polymeric nanoparticles have tremendous potential either as carriers or markers in treatment of diseases or diagnostics in biomedical applications. Finding the optimal conditions for effective intracellular delivery of the payload to the place of interest is still a big challenge. The particles have to overcome the cell membrane representing a barrier. Here, we investigated the uptake in HeLa cells of fluorescent polystyrene particles with different size and surface charge. Particles stabilized with the non-ionic surfactant Lutensol AT50® (132 nm, 180 nm, 242 nm, 816 nm, 846 nm) were synthesized via dispersion polymerization. Cationic particles (120 nm, 208 nm, 267 nm, 603 nm) were obtained by a combination of miniemulsion and seed dispersion polymerization using cationic surfactant (cetyltrimethylammonium chloride (CTMA-Cl). The particle uptake into HeLa cells was studied by confocal laser scanning microscopy and flow cytometry. Non-ionic particles were - independent of their size - taken up by cells only at a barely detectable level thus aggravating a quantitative comparison. The uptake of positively charged particles was substantially higher and therefore further investigation keeping constant one of these parameters: either material amount or particles number or total interaction surface area. It was found that the uptake rather depends on the total amount of polymeric material present in the media than on the number of particles. The total particle’s surface area does not correlate linearly with the uptake, thus indicating that there is no direct dependency between the total surface area and the cellular endocytotic process to overcome the biobarrier “cell membrane”. A new uptake mechanism is found which can be described as an excavator shovel like mechanism. It is a kind of macropinocytosis dependent on actin filaments as well as dynamin, but is clathrin-independent.
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Concepts
Emulsion, Cell, Electric charge, Endocytosis, Protein, Cell biology, Surfactant, Cell membrane
MeSH headings
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