Oligonucleotide-protamine-albumin nanoparticles: preparation, physical 
properties, and intracellular distribution

Vogel, Vitali; Lochmann, Dirk; Weyermann, Jörg; Mayer, Gottfried; Tziatzios, Christos; van den Broek, Jacomina A.; Haase, Winfried; Wouters, Daan; Schubert, Ulrich S.; Kreuter, Jörg; Zimmer, Andreas; Schubert, Dieter

doi:10.1016/j.jconrel.2004.11.029

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Oligonucleotide-protamine-albumin nanoparticles: preparation, physical properties, and intracellular distribution

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Haase, Winfried
Department of Structural Biology, Max Planck Institute of Biophysics, Max Planck Society;

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Citation

Vogel, V., Lochmann, D., Weyermann, J., Mayer, G., Tziatzios, C., van den Broek, J. A., et al. (2005). Oligonucleotide-protamine-albumin nanoparticles: preparation, physical properties, and intracellular distribution. Journal of Controlled Release, 103(1), 99-111. doi:10.1016/j.jconrel.2004.11.029.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0024-DA2C-9

Abstract

Oligodesoxynucleotides (ODNs) or the corresponding phosphorothioates (PTOs) spontaneously form spherical nanoparticles (“proticles”) with protamine in aqueous solutions. The proticles can cross cellular membranes and release the ODNs within the cells. Thus, they represent a potential drug delivery system. The major disadvantages of this system are a lack of stability in salt solutions and its inability to also release PTOs. The present study shows, using PTOs and protamine free base, that these shortcomings can be eliminated by the addition of human serum albumin (HSA) as a third component to the starting mixture. The “ternary” proticles thus obtained contain maximally a few percent of the HSA that was originally present. Nevertheless, they differ from the previously studied “binary” proticles: (1) They are stable in salt solutions for at least several hours. (2) They show a high cellular uptake into murine fibroblasts, and they readily release the PTOs after uptake. The ternary proticles therefore represent a considerable improvement over binary proticles for use as drug delivery systems.