The potency of nano- and micro-particles, loaded with drugs, genes, and/or diagnostics, is frequently depending upon their morphology adopted in a biological relevant environment. Freeze-fracture electron microscopy as a cryo-fixation, replica TEM method is a powerful technique to monitor self-assembling of lipid-, polymer-, as well as protein/peptide-based carriers encapsulating drug-, gene-, and imaging molecules. Since its resolution, determined by the particle size of the evaporation layer, is 2 nm for periodical structures we are able to characterize such carriers on a nano-size resolution scale [1-3]. Freeze-fracture electron microscopy allows not only the characterization of nano- and micro-particles suitable for therapy and imaging but also is the method of choice to study their fate related to their pay load, application milieu [4], and during their interaction with cells. Furthermore, ff-em allows observing superstructure transformation from bilayer to non-bilayer structures such as micelles and hexagonal as well as cubic lipid phases [5].

Using freeze-fracture electron microscopy we studied the morphology of a wide variety of nano- and micro particles suitable as carriers for diagnostics as well as therapeutics. These studies include quantum dots (free and coupled to drug-loaded immunoliposomes), micelles (spherical-, disc-, and worm-type micelles) [6], small unilamellar liposome [7], multilamellar liposome, niosomes [8], cationic liposome / DNA complexes [9-10], polymer- or lipid-stabilized gas bubbles [11], cochleate cylinder, depofoam particles, and drug crystals. Furthermore, nano-size domains have been observed in liposomal bilayer caused by amphiphatic drugs [6]. Additionally, parallel studies combining morphology and transfection activity reveled that hexagonal lipid phases show high transfection activity in vitro while high in vivo transfection activity is related to small complexes with some protrusions [10]. We also recorded the cell interaction of selected carries.

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[5] A. Angelova et al. J. Phys. Chem. B. 109 (8) (2005) 3089.

[6] V. P. Torchilin et al. PNAS (2003) 100 (4) 1972.

[7] V. P. Torchilin et al. PNAS (2003) 100 (10) 603.

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[9] B. Sternberg et al. FEBS-Letters 356 (1994) 361.

[10] B. Sternberg et al. Biochim. Biophys. Acta 1375 (1998) 1375.

[11] C. Brancewicz et al. J. Disp. Sci. & Techn. 27:5 (2006) 761.