The analysis of nanomaterials in pharmaceutical or cosmetic preparations is an important aspect both in formulation development and quality control of marketed products. Despite the increased popularity of nanoparticulate compounds especially in dermal preparations such as emulsions, methods and protocols of analysis for the characterization of such systems are scarce. This work combines an original sample preparation procedure along with different methods of analytical electron microscopy for the comprehensive analysis of fluid or semi-solid dermal preparations containing nanoparticulate material. Energy-filtered transmission electron microscopy, energy-dispersive X-ray spectroscopy, electron energy loss spectroscopy and high resolution imaging were performed on model emulsions and a marketed product to reveal different structural aspects of both the emulsion bulk phase and incorporated nanosized material. An innovative analytical approach for the determination of the physical stability of the emulsion under investigation is presented. Advantages and limitations of the employed analytical imaging techniques are highlighted.
References
[1]
Mueller-Goymann, C.C. Physicochemical characterization of colloidal drug delivery systems such as reverse micelles, vesicles, liquid crystals and nanoparticles for topical administration. Eur. J. Pharm. Biopharm. 2004, 58, 343–356, doi:10.1016/j.ejpb.2004.03.028.
[2]
Klang, V.; Valenta, C.; Matsko, N.B. Electron microscopy of pharmaceutical systems. Micron 2012, 44, 45–74.
[3]
Egerton, R.F. Electron Energy-Loss Spectroscopy in the Electron Microscope; Plenum Press: New York, NY, USA, 1986.
[4]
Williams, D.B.; Carter, C.B. Transmission Electron Microscopy: A Textbook for Materials Science; Springer: New York, NY, USA, 2009.
[5]
Hitchcock, A.P.; Dynes, J.J.; Johansson, G.; Wang, J.; Botton, G. Comparison of NEXAFS microscopy and TEM-EELS for studies of soft matter. Micron 2008, 39, 741–748, doi:10.1016/j.micron.2007.09.010.
[6]
Kim, G.; Sousa, A.; Meyers, D.; Shope, M.; Libera, M. Diffuse polymer interfaces in lobed nanoemulsions preserved in aqueous media. J. Am. Chem. Soc. 2006, 128, 6570–6571.
[7]
Yakovlev, S.; Libera, M. Dose-limited spectroscopic imaging of soft materials by low-loss EELS in the scanning transmission electron microscope. Micron 2008, 39, 734–740, doi:10.1016/j.micron.2007.10.019.
[8]
Kline, R.; DeLongchamp, D.M.; Fischer, D.A.; Lin, E.K.; Richter, L.J.; Chabinyc, M.L.; Toney, M.; Heeney, M.; McCulloch, M. Critical Role of Side-Chain Attachment Density on the Order and Device Performance of Polythiophenes. Macromolecules 2007, 40, 7960–7965.
[9]
Horiuchi, S.; Hanada, T.; Ebisawa, M.; Matsuda, Y.; Kobayashi, M.; Takahara, A. Contamination-Free Transmission Electron Microscopy for High-Resolution Carbon Elemental Mapping of Polymers. ACS Nano 2009, 3, 1297–1304, doi:10.1021/nn9001598.
[10]
Horiuchi, S.; Hanada, T.; Izu, N.; Matsubara, I. Electron microscopy investigations of the organization of cerium oxide nanocrystallites and polymers developed in polyvinylpyrrolidone-assisted polyol synthesis process. J. Nanopart. Res. 2012, 14, 734, doi:10.1007/s11051-012-0734-7.
[11]
Klang, V.; Schwarz, J.C.; Matsko, N.; Rezvani, E.; El-Hagin, N.; Wirth, M.; Valenta, C. Semi-Solid Sucrose Stearate-Based Emulsions as Dermal Drug Delivery Systems. Pharmaceutics 2011, 3, 275–306, doi:10.3390/pharmaceutics3020275.
[12]
Matsko, N.; Letofsky-Papst, I.; Albu, M.; Mittal, V. An analytical technique to extract the surface information of negatively stained or heavy-metal shadowed organic materials within the TEM. Micros. Microanal. 2013. in press.
[13]
Schaffer, B.; Grogger, W.; Kothleitner, G. Automated spatial drift correction for EFTEM image series. Ultramicroscopy 2004, 102, 27–36, doi:10.1016/j.ultramic.2004.08.003.
[14]
Klang, V.; Matsko, N.B.; Valenta, C.; Hofer, F. Electron microscopy of nanoemulsions: An essential tool for characterisation and stability assessment. Micron 2012, 43, 85–103, doi:10.1016/j.micron.2011.07.014.
[15]
Adrian, M.; Dubochet, J.; Lepault, J.; McDowall, A.W. Cryo-electron microscopy of viruses. Nature 1984, 308, 32–36, doi:10.1038/308032a0.
[16]
？aplovi？ová, M.; Billik, P.; ？aplovi？, L.; Brezová, V.; Turáni, T.; Plesch, G.; Fejdi, P. On the true morphology of highly photoactive anatase TiO2 nanocrystals. Appl. Catal. B 2012, 117-118, 224–235, doi:10.1016/j.apcatb.2012.01.010.
[17]
Brenner, S.; Horne, R.W. A negative staining method for high resolution electron microscopy of viruses. Biochim. Biophys. Acta 1959, 34, 103–110, doi:10.1016/0006-3002(59)90237-9.
[18]
Hayat, M.A. Principles and Techniques of Electron Microscopy: Biological Application; Cambridge University Press: New York, NY, USA, 2000.
[19]
Hayat, M.A.; Miller, S.E. Negative Staining; McGraw-Hill: New York, NY, USA, 1990.
[20]
De Carlo, S.; Harris, J.R. Negative staining and cryo-negative staining of macromolecules and viruses for TEM. Micron 2011, 42, 117–131, doi:10.1016/j.micron.2010.06.003.
[21]
Daniels, H.R.; Brydson, R.; Brown, A.; Rand, B. Quantitative valence Plasmon mapping in TEM: Viewing physical properties at the nanoscale. Ultramicroscopy 2003, 96, 547–558, doi:10.1016/S0304-3991(03)00115-3.
[22]
Hofer, F.; Grogger, W.; Kothleitner, G.; Warbichler, P. Quantitative analysis of EFTEM elemental distribution images. Ultramicroscopy 1997, 67, 83–103, doi:10.1016/S0304-3991(96)00106-4.
[23]
Leapman, R.D. Microbeam Analysis; San Francisco Press: San Francisco, CA, USA, 1986; pp. 187–191.
[24]
Egerton, R.F. Electron energy-loss spectroscopy in the TEM. Rep. Prog. Phys. 2009, 72, doi:10.1088/0034-4885/72/1/016502.
