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Transmission Electron Microscopy of Lipid Vesicles for Drug Delivery: Comparison between Positive and Negative Staining

Published online by Cambridge University Press:  22 June 2010

Valentina Bello ,
Giovanni Mattei ,
Paolo Mazzoldi ,
Nicoletta Vivenza ,
Paolo Gasco ,
Jean Marc Idee ,
Caroline Robic  and
Elisabetta Borsella
Valentina Bello*
Affiliation:
Department of Physics, University of Padova, via Marzolo 8, I-35131 Padova, Italy
Giovanni Mattei
Affiliation:
Department of Physics, University of Padova, via Marzolo 8, I-35131 Padova, Italy
Paolo Mazzoldi
Affiliation:
Department of Physics, University of Padova, via Marzolo 8, I-35131 Padova, Italy
Nicoletta Vivenza
Affiliation:
Nanovector S.r.l., via Livorno, 60, I-10144 Torino, Italy
Paolo Gasco
Affiliation:
Nanovector S.r.l., via Livorno, 60, I-10144 Torino, Italy
Jean Marc Idee
Affiliation:
Guerbet, 15 rue des Vanesses, Zone Paris Nord I, 93420 Villepinte (Paris), France
Caroline Robic
Affiliation:
Guerbet, 15 rue des Vanesses, Zone Paris Nord I, 93420 Villepinte (Paris), France
Elisabetta Borsella
Affiliation:
ENEA, Dept. FIM, via E. Fermi 45, I-00044 Frascati (Rome), Italy
*
Corresponding author. E-mail: bello@padova.infm.it
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Abstract

Lipid-containing nanostructures, in the form of solid lipid nanoparticles or iron oxide nanoparticles (NPs) coated with a lipid shell, were used as case studies for assessing and optimizing staining for transmission electron microscopy structural and compositional characterization. These systems are of paramount importance as drug delivery systems or as bio-compatible contrast agents. In particular, we have treated the systems with a negative (phospshotungstic acid) or with a positive (osmium tetroxide) staining agent. For iron-oxide NPs coated with the lipid shell, negative staining was more efficient with respect to the positive one. Nevertheless, in particular cases the combination of the two staining procedures provided more complete morphological and compositional characterization of the particles.

Keywords

lipid nanoparticlesUSPIOstaining processTEM
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 16 , Issue 4 , August 2010 , pp. 456 - 461
Copyright
Copyright © Microscopy Society of America 2010

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References

REFERENCES

Al-Haj, N. & Rasedee, A. (2009). Solid lipid nanoparticles preparation and characterization. Intern J Pharm 5(1), 90–93.CrossRefGoogle Scholar
Azevedo, E.G., Ramaldes, G.A., Frèzard, F., Vilela, J.M., Andrade, M.S. & Ferreira, L.A.M. (2005). Characterization of liposomes containing 5-fluorouracil in hydrophilic gel using atomic force microscopy. Microsc Microanal 11(S3), 62–65.CrossRefGoogle Scholar
Bangham, A.D. & Horne, R.W. (1964). Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. J Mol Biol 8, 660–668.CrossRefGoogle ScholarPubMed
Bargoni, A., Cavalli, R., Caputo, O., Fundarò, A., Gasco, M.R. & Zara, G.P. (1998). Solid lipid nanoparticles in lymph and plasma after duodenal administration to rats. Pharm Res 15(5), 745–750.CrossRefGoogle ScholarPubMed
Brioschi, A.M., Calderoni, E., Pradotto, L.G., Guido, M., Strada, A., Zenga, F., Benech, C.A., Serpe, L., Zara, G.P., Musicanti, C., Ducati, A., Gasco, M.R. & Mauro, A. (2009). Solid lipid nanoparticles carrying oligonucleotides inhibit vascular endothelial growth factor expression in rat glioma models. J Nanoneurosci 1, 65–74.CrossRefGoogle Scholar
Cho, S.M., Lee, H.Y. & Kim, J.C. (2007). Characterization and in-vitro permeation study of stearic acid nanoparticles containing hinokitiol. J Am Chem Soc 84, 859–863.Google Scholar
Corot, T.C., Robert, P., Idee, J.M. & Port, M. (2006). Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58, 1471–1504.CrossRefGoogle ScholarPubMed
Dubertret, B., Skourides, P., Norris, D.J., Noireaux, V., Brivanlou, A.H. & Libchaber, A. (2002). In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298, 1759–1762.CrossRefGoogle ScholarPubMed
Dubes, A., Parrot-Lopez, H., Abdelwahed, W., Degobert, G., Fessi, H., Shahgaldian, P. & Coleman, A.W. (2003). Scanning electron microscopy and atomic force microscopy imaging of solid lipid nanoparticles derived from amphiphilic cyclodextrins. Eur J Pharm Biopharm 55, 279–282.CrossRefGoogle ScholarPubMed
Garg, A. & Kokkoli, E. (2005). Characterizing particulate drug-delivery carriers with atomic force microscopy. IEEE Eng Med Biol 24 (1), 87–95.CrossRefGoogle ScholarPubMed
Gasco, M.R. (2007). Lipid nanoparticles: Perspectives and challenges. Adv Drug Deliv Rev 59, 377–378.CrossRefGoogle Scholar
Igartua, M., Saulnier, P., Heurtault, B., Pech, B., Proust, J.E., Pedraz, J.L. & Benoit, J.P. (2002). Development and characterization of solid lipid nanoparticles loaded with magnetite. Intern J Pharm 233, 149–157.CrossRefGoogle ScholarPubMed
Jores, K., Mehnert, W., Dreschsler, M., Bunjes, H., Johann, C. & Mader, K. (2004). Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. J Control Release 95, 217–227.CrossRefGoogle ScholarPubMed
Melchior, V., Hollingshead, C.J. & Cahoon, M.E. (1980). Stacking in lipid vesicle-tubulin mixtures is an artifact of negative staining. J Cell Biol 86, 881–884.CrossRefGoogle ScholarPubMed
Morel, S., Terreno, E., Ugazio, E., Aime, S. & Gasco, M.R. (1998). NMR relaxometric investigations of solid lipid nanoparticles (SLN) containing gadolinium(III) complexes. Eur J Pharm Biopharm 45, 157–163.CrossRefGoogle ScholarPubMed
Muller, R.H. & Keck, C.M. (2004). Challenges and solutions for the delivery of biotech drugs—A review of drug nanocrystal technology and lipid nanoparticles. J Biotech 113, 151–170.CrossRefGoogle ScholarPubMed
Muller, R.H., Mader, K. & Gohla, S. (2000). Solid lipid nanoparticles (SLN) for controlled drug delivery—A review of the state of the art. Eur J Pharm Biopharm 50, 161–177.CrossRefGoogle ScholarPubMed
Peira, E., Marzola, P., Podio, V., Aime, S., Sbarbati, A. & Gasco, M.R. (2003). In vitro and in vivo study of solid lipid nanoparticles loaded with superparamagnetic iron oxide. J Drug Target 11(1), 19–24.CrossRefGoogle ScholarPubMed
Podio, V., Zara, G.P., Carazzone, M., Cavalli, R. & Gasco, M.R. (2000). Biodistribution of stealth and non-stealth solid lipid nanospheres after intravenous administration to rats. J Pharm Pharmacol 52, 1057–1063.CrossRefGoogle ScholarPubMed
Riemersma, J.C. (1963). Osmium tetroxide fixation of lipids: Nature of the reaction products. J Histochem Cytochem 11, 436–441.CrossRefGoogle Scholar
Riemersma, J.C. & Booij, H.L. (1962). The reaction of osmium tetroxide with lecithin: Application of staining procedures. J Histochem Cytochem 10, 89–95.CrossRefGoogle Scholar
Shah, K.A., Date, A.A., Joshi, M.D. & Patravale, V.B. (2007). Solid lipid nanoparticles (SLN) of tretinoin: Potential in topical delivery. Intern J Pharm 345, 163–171.CrossRefGoogle ScholarPubMed
Trotta, M., Cavalli, R., Carlotti, M.E., Battaglia, L. & Debernardi, F. (2005). Solid lipid micro-particles carrying insulin formed by solvent-in-water emulsion-diffusion technique. Intern J Pharm 288, 281–288.CrossRefGoogle ScholarPubMed
Ugazio, E., Cavalli, R. & Gasco, M.R. (2002). Incorporation of cyclosporine A in solid lipid nanoparticles (SLN). Intern J Pharm 241, 341–344.CrossRefGoogle ScholarPubMed
Weiss, J., Decker, E.A., McClements, D.J., Kristbergsson, K., Helgason, T. & Awad, T. (2008). Solid lipid nanoparticles as delivery systems for bioactive food components. Food Biophys 3, 146–154.CrossRefGoogle Scholar