Nair Praful R, Karthick S A, Spinler Kyle R, Vakili Mohammad R, Lavasanifar Afsaneh, Discher Dennis E
Biophysical Engineering Labs - NanoBioPolymers Lab, School of Engineering & Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
Nanomedicine (Lond). 2016 Jun;11(12):1551-69. doi: 10.2217/nnm-2016-0007. Epub 2016 May 13.
In order to improve the delivery of aromatic drugs by micellar assemblies, and particularly by long and flexible filomicelles, aromatic groups were integrated into the hydrophobic block of a degradable diblock copolymer.
MATERIALS & METHODS: Aromatic filomicelles were formed by self-directed assembly of amphiphilic diblock copolymer PEG-PBCL with suitable block ratios. Worm-like filomicelles with an aromatic core were loaded with a common chemotherapeutic, Paclitaxel, for tests of release as well as effects on cancer cell lines in vitro and in vivo.
Aromatic filomicelles loaded more Paclitaxel than analogous aliphatic systems. Cell death and aneuploidy of surviving cells (which indicates toxicity) were highest for carcinoma lines treated in vitro with the new filomicelles. Initial tests in vivo also suggest more potent tumor shrinkage.
Flexible filomicelles with an aromatic core form an efficient drug delivery system that leads to higher cell death than previously reported systems, while inducing aneuploidy in surviving cells.
为了改善通过胶束组装体,特别是通过长且柔性的丝状胶束来递送芳香族药物,将芳香基团整合到可降解二嵌段共聚物的疏水嵌段中。
通过具有合适嵌段比例的两亲性二嵌段共聚物PEG-PBCL的自组装形成芳香族丝状胶束。将具有芳香核的蠕虫状丝状胶束负载常用化疗药物紫杉醇,用于体外和体内的释放测试以及对癌细胞系的作用测试。
芳香族丝状胶束比类似的脂肪族体系负载更多的紫杉醇。在用新的丝状胶束进行体外处理的癌细胞系中,细胞死亡和存活细胞的非整倍体(表明毒性)最高。体内初步测试也表明肿瘤缩小更显著。
具有芳香核的柔性丝状胶束形成了一种高效的药物递送系统,与先前报道的系统相比,该系统导致更高的细胞死亡,同时在存活细胞中诱导非整倍体。