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
Institut für Biophysik, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, Haus 74, 60590 Frankfurt am Main, Germany.
J Control Release. 2005 Mar 2;103(1):99-111. doi: 10.1016/j.jconrel.2004.11.029. Epub 2005 Jan 8.
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.
在水溶液中，寡脱氧核苷酸（ODNs）或相应的硫代磷酸酯（PTOs）能与鱼精蛋白自发形成球形纳米颗粒（“原颗粒”）。这些原颗粒可穿过细胞膜并在细胞内释放ODNs。因此，它们代表了一种潜在的药物递送系统。该系统的主要缺点是在盐溶液中缺乏稳定性，且无法释放PTOs。本研究表明，使用PTOs和游离鱼精蛋白碱，通过向起始混合物中添加人血清白蛋白（HSA）作为第三种成分，可以消除这些缺点。由此获得的“三元”原颗粒最多含有最初存在的HSA的百分之几。然而，它们与先前研究的“二元”原颗粒不同：（1）它们在盐溶液中至少能稳定存在几个小时。（2）它们在小鼠成纤维细胞中具有较高的细胞摄取率，并且摄取后能轻易释放PTOs。因此，三元原颗粒作为药物递送系统比二元原颗粒有了显著改进。
