Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Biomaterials. 2012 Nov;33(32):8122-30. doi: 10.1016/j.biomaterials.2012.07.031. Epub 2012 Aug 4.
We developed a paclitaxel-conjugated polymeric micelle, ABP-PEG3.5k-Paclitaxel (APP) consisting of poly (ethylene glycol) (PEG) and arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP) for the co-delivery of gene and drug. The APP polymer self-assembled into cationic polymeric micelles with a critical micelle concentration (CMC) value of approximately 0.062 mg/mL, which was determined from measurements of the UV absorption of pyrene. The micelles have an average size of about 3 nm and a zeta potential of about +14 mV. Due to the positive surface charge, APP micelles formed polyplexes with plasmid DNA approximately 200 nm in diameter. The luciferase gene and mouse interleukin-12 (IL-12) gene was used to monitor gene delivery potency. APP polyplexes showed increased gene delivery efficiency and cellular uptake with higher anticancer potency than paclitaxel alone. These results demonstrate that an APP micelle-based delivery system is well suitable for the co-delivery of gene and drug.
我们开发了一种紫杉醇偶联的聚合物胶束,ABP-PEG3.5k-紫杉醇(APP),由聚乙二醇(PEG)和精氨酸接枝聚(胱胺二丙烯酰胺-二氨基己烷)(ABP)组成,用于基因和药物的共递送。APP 聚合物自组装成具有临界胶束浓度(CMC)值约为 0.062mg/mL 的阳离子聚合物胶束,这是通过测量芘的紫外吸收来确定的。胶束的平均粒径约为 3nm,zeta 电位约为+14mV。由于表面带正电荷,APP 胶束与直径约为 200nm 的质粒 DNA 形成了聚合物复合物。荧光素酶基因和小鼠白细胞介素-12(IL-12)基因被用来监测基因递送效力。APP 聚合物复合物显示出比单独使用紫杉醇更高的基因递送效率和细胞摄取率,以及更高的抗癌效力。这些结果表明,基于 APP 胶束的递药系统非常适合基因和药物的共递送。