Oligonucleotide–protamine–albumin nanoparticles: preparation, physical properties, and intracellular distribution
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Vogel, Vitali; Lochmann, Dirk; Weyermann, Joerg; Mayer, Gottfried; Tziatzios, Christos; van den Broek, Jacomina A.; Haase, Winfried; Wouters, Daan; Schubert, Ulrich S.; Kreuter, Joerg; Zimmer, Andreas; Schubert, Dieter
- Abstract:
- Oligodesoxynucleotides (ODNs) or the corresponding phosphorothioates (PTOs) spontaneously form spherical nanoparticles
(bproticlesQ) 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 bternaryQ proticles thus obtained contain maximally a few percent of the HSA that was originally present.
Nevertheless, they differ from the previously studied bbinaryQ 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.
- Year:
- 2005
- Type of Publication:
- Article
- Keywords:
- Nanoparticles; Phosphorothioates; Protamine; Human serum albumin HSA; Cellular release
- Journal:
- Journal of Controlled Release
- Volume:
- 103
- Pages:
- 99 - 111