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Binding of positively and negatively charged micro- and nanoparticles to an epithelial and endothelial cell model

By Bettina Luser


nicht angegebenThe most prominent biological barriers encountered by particulate drug carriers upon administration to the human body are represented by epithelial and endothelial cells. Hence, a strong interaction with these tissues is essential to prolong the residence time of particles in the body or to achieve their absorption. Aside from surface modification with biorecognitive ligands, [1] coating of colloids with cationic polyelectrolytes has been discussed as a potential strategy to enhance the interaction with epithelial and endothelial cells. [1, 2] This rationale is based on the observation that all cell types of multicellular organisms are characterized by negatively charged cell surfaces. [3] The charges in the cell membrane largely derive from sialic acid carboxy groups and phosphates of phospholipid head groups. Aside from negative groups, cationic charges also exist which probably can be attributed to ε-amino groups of lysine side chains of membrane proteins. [3] It is not clear whether these charged moieties in the plasma membrane are evenly distributed or clustered, but generally negative groups seem to prevail. As indicated by several studies, ionic interactions between the particle surface and the cell might indeed mediate improved bioadhesion.\ud Thiele et al. showed that clearly higher quantities of PLL-coated PS microspheres were associated with and internalized by Antigen-Presenting Cells (APCs) in vitro as compared with negatively charged beads. [4] Moreover, positively charged particles were phagocytosed in endosomes which showed considerable interactions between the particle surface and the vesicle membrane. [5]\ud That positively charged carriers are also characterized by an altered biodistribution as compared to their negatively charged counterparts has been shown in in vivo studies. Polystyrene latices sized 1.3 μm, which had been surface modified with polylysyl gelatine, were preferentially located in the lung 15 min after injection. [6] However, it was not clear if this altered biodistribution was essentially due to altered bioadhesion of positively charged colloids. Rather than that the authors argued that positively charged particles might be more prone to the formation of aggregates in whole blood. These aggregates might subsequently be trapped in the extensive capillary bed of the lung. More concrete evidence of enhanced bioadhesion of positively charged particles to the endothelium was provided by Labhasetwar et al. [2] PLGA nanoparticles sized ~100 nm that had been coated with the cationic excipient dimethyl dioctadecyl ammonium bromide (DDAB) delivered 7-10 fold higher drug levels to isolated artery segments ex vivo than negatively charged colloids. Even more interesting in regards to potential targeting via charge, Thurston et al. reported that cationic liposomes preferentially bind to and are taken up by angiogenic endothelial cells in mouse tumor models and in a mouse model of chronic inflammation. [7] Thus, modifying the surface charge of particles might not only lead to increased bioadhesion, but might also represent an approach for targeting to specific cell populations.\ud From most studies in the literature it is difficult to deduce whether bioadhesion of charged particles is mediated by the charge itself, by proteins specifically adsorbed from serum or by other factors such as aggregate formation in whole blood. In this study, carboxylated PS nano- and microspheres and the same particles coated with the cationic polyelectrolyte poly(ethylenimine) (PEI) will serve as model colloids, since they resemble micro- and nanoparticulate drug carriers in size and charge.\ud Caco-2 and human umbilical vein endothelial cell (HUVEC) monolayers will be employed as epithelial and endothelial cell models respectively which are highly relevant for drug delivery. Using these particle and cell types in a controllable in vitro setting, it will be investigated if positively charged carriers are indeed characterized by higher bioadhesion than their negative counterparts.\u

Topics: 30.30 Naturwissenschaften in Beziehung zu anderen Fachgebieten, Bindung / positiv / negativ / Mikropartikel / Nanopartikel / epithelial / endothelial, binding / positively / negatively / microparticles / nanoparticles / epithelial / endothelial
Year: 2012
OAI identifier: oai:othes.univie.ac.at:20110
Provided by: OTHES
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