Department of Pharmaceutics and Biopharmacy, Philipps-Universität Marburg, Ketzerbach 63, D-35037 Marburg, Germany.
Int J Pharm. 2011 Apr 4;407(1-2):190-6. doi: 10.1016/j.ijpharm.2011.01.028. Epub 2011 Jan 21.
The aim of this study was to formulate nanoparticles from three different hyperbranched polymers, namely an unmodified dendritic polyester (Boltorn H40™), a lipophilic, fatty acid modified dendritic polymer (Boltorn U3000™) and an amphiphilic dendritic polymer (Boltorn W3000™) for drug delivery of paclitaxel and to investigate their properties. A solvent displacement method allowed preparation of nanoparticles from all three hyperbranched polymers. Nanoparticle sizes ranged from 70 to 170 nm. The lipophilic Boltorn U3000™ formed the biggest nanoparticles and the amphiphilic Boltorn W3000™ formed the smallest ones. Nanoparticles of amphiphilic Boltorn W3000™ displayed only a slightly negative zeta potential, while more negative zeta potentials were measured for nanoparticles based on the other two polymers. Degradation profiles were investigated by short time pH-stat titration. Boltorn H40™ showed a faster degradation rate then the two other fatty acid containing polymers. For Boltorn H40™, degradation rate was also investigated in longer term mass loss studies resulting in 30% degradation during 3 weeks. Cytotoxicity of the nanoparticles was studied by MTT assay displaying low cytotoxicity for all three polymers. All three types of nanoparticles were loaded with paclitaxel and their release profiles were studied. Sizes and zeta potentials remained stable after loading and did not change significantly. These three types of hyperbranched polymers show potential as nanoparticulate delivery systems and should be further studied. Due to their high loading efficiency, Boltorn U3000 and W3000 represent the most interesting candidates.
本研究的目的是从三种不同的超支化聚合物中制备纳米粒，即未经修饰的树枝状聚酯（Boltorn H40™）、亲脂性脂肪酸修饰的树枝状聚合物（Boltorn U3000™）和两亲性树枝状聚合物（Boltorn W3000™），用于紫杉醇的药物传递，并研究它们的性质。溶剂置换法允许从所有三种超支化聚合物中制备纳米粒。纳米粒的粒径范围为 70 至 170nm。亲脂性的 Boltorn U3000™形成了最大的纳米粒，而两亲性的 Boltorn W3000™形成了最小的纳米粒。两亲性 Boltorn W3000™纳米粒的表面仅带轻微的负 ζ 电位，而基于其他两种聚合物的纳米粒的 ζ 电位则更负。通过短时间 pH -stat 滴定研究降解曲线。Boltorn H40™的降解速度比其他两种含脂肪酸的聚合物更快。对于 Boltorn H40™，还在更长时间的质量损失研究中研究了降解速率，结果在 3 周内降解了 30%。通过 MTT 测定法研究了纳米粒的细胞毒性，显示出所有三种聚合物均具有低细胞毒性。所有三种类型的纳米粒均负载了紫杉醇，并研究了它们的释放曲线。负载后粒径和 ζ 电位保持稳定，没有明显变化。这三种类型的超支化聚合物显示出作为纳米递药系统的潜力，应进一步研究。由于 Boltorn U3000 和 W3000 具有较高的载药效率，它们是最有前途的候选药物。
