In vitro adsorption of plasma proteins onto the surface (charges) modified-submicron emulsions for intravenous administration

Surface (charge) modified submicron emulsions (cationic and anionic) were prepared following the well established combined emulsification techniques and characterized for their droplet size distribution and surface charge. The effect of these emulsions on in vitro adsorption of plasma proteins was investigated by means of two dimensional polyacrylamide gel electrophoresis (2D PAGE). The presence of poloxamer 188 in tested emulsions effectively eliminated the adsorption of the larger proteins like immunoglobulins, fibrinogen, etc. However, depending on the type of surface charges, the smaller proteins such as apolipoproteins and albumin were almost completely adsorbed onto the submicron emulsions. Indeed, when compared to marketed lipofundin MCT 10%-and deoxycholic acid-based anionic emulsions, the adsorption of apolipoprotein, especially apoA-I was approximately three times more on stearylamine-and oleylamine-based cationic emulsions and oleic acid-based anionic emlusions. In addition, the ratio between the apoA-I and apoA-IV was found to be 1 for lipofundin MCT 10% whereas it was about 0.26 for deoxycholic acid-based anionic emulsion and above 5 for oleic acid-based anionic emulsions and cationic emulsions. This indicates that emulsions having similar surface/interfacial charge imparted by different anion-forming stabilizers (oleic or deoxycholic acids) exhibited markedly different protein adsorption patterns. (C) 2004 Elsevier B.V. All rights reserved.