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Modification of composition of a nanoemulsion with different cholesteryl ester molecular species: Effects on stability, peroxidation, and cell uptake

Original Research

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Authors: Cristina P Almeida, Carolina G Vital, Thais C Contente, et al

Published Date September 2010 Volume 2010:5 Pages 679 - 686
DOI: http://dx.doi.org/10.2147/IJN.S12293

Cristina P Almeida1, Carolina G Vital1, Thais C Contente1, Durvanei A Maria2, Raul C Maranhão1,3
1Lipid Metabolism Laboratory, Heart Institute (InCor), Medical School Hospital, 2Biochemistry and Biophysics Laboratories, Butantan Institute, 3Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

Purpose: Use of lipid nanoemulsions as carriers of drugs for therapeutic or diagnostic purposes has been increasingly studied. Here, it was tested whether modifications of core particle constitution could affect the characteristics and biologic properties of lipid nanoemulsions.
Methods: Three nanoemulsions were prepared using cholesteryl oleate, cholesteryl stearate, or cholesteryl linoleate as main core constituents. Particle size, stability, pH, peroxidation of the nanoemulsions, and cell survival and uptake by different cell lines were evaluated.
Results: It was shown that cholesteryl stearate nanoemulsions had the greatest particle size and all three nanoemulsions were stable during the 237-day observation period. The pH of the three nanoemulsion preparations tended to decrease over time, but the decrease in pH of cholesteryl stearate was smaller than that of cholesteryl oleate and cholesteryl linoleate. Lipoperoxidation was greater in cholesteryl linoleate than in cholesteryl oleate and cholesteryl stearate. After four hours’ incubation of human umbilical vein endothelial cells (HUVEC) with nanoemulsions, peroxidation was minimal in the presence of cholesteryl oleate and more pronounced with cholesteryl linoleate and cholesteryl stearate. In contrast, macrophage incubates showed the highest peroxidation rates with cholesteryl oleate. Cholesteryl linoleate induced the highest cell peroxidation rates, except in macrophages. Uptake of cholesteryl oleate nanoemulsion by HUVEC and fibroblasts was greater than that of cholesteryl linoleate and cholesteryl stearate. Uptake of the three nanoemulsions by monocytes was equal. Uptake of cholesteryl oleate and cholesteryl linoleate by macrophages was negligible, but macrophage uptake of cholesteryl stearate was higher. In H292 tumor cells, cholesteryl oleate showed the highest uptakes. HUVEC showed higher survival rates when incubated with cholesteryl stearate and smaller survival with cholesteryl linoleate. H292 survival was greater with cholesteryl stearate.
Conclusion: Although all three nanoemulsion types were stable for a long period, considerable differences were observed in size, oxidation status, and cell survival and nanoemulsion uptake in all tested cell lines. Those differences may be helpful in protocol planning and interpretation of data from experiments with lipid nanoemulsions.

Keywords: emulsions, cholesterol, drug vehicles, lipoprotein receptors, solid lipid nanoparticles






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