Cai Shenshen, Vijayan Kandaswamy, Cheng Debbie, Lima Eliana M, Discher Dennis E
Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Pharm Res. 2007 Nov;24(11):2099-109. doi: 10.1007/s11095-007-9335-z. Epub 2007 Jun 13.
Worm-like and spherical micelles are both prepared here from the same amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly (epsilon-caprolactone) (PEO [5 kDa]-PCL [6.5 kDa]) in order to compare loading and delivery of hydrophobic drugs.
Worm-like micelles of this degradable copolymer are nanometers in cross-section and spontaneously assemble to stable lengths of microns, resembling filoviruses in some respects and thus suggesting the moniker 'filomicelles'. The highly flexible worm-like micelles can also be sonicated to generate kinetically stable spherical micelles composed of the same copolymer.
The fission process exploits the finding that the PCL cores are fluid, rather than glassy or crystalline, and core-loading of the hydrophobic anticancer drug delivery, paclitaxel (TAX) shows that the worm-like micelles load and solubilize twice as much drug as spherical micelles. In cytotoxicity tests that compare to the clinically prevalent solubilizer, Cremophor EL, both micellar carriers are far less toxic, and both types of TAX-loaded micelles also show fivefold greater anticancer activity on A549 human lung cancer cells.
PEO-PCL based worm-like filomicelles appear to be promising pharmaceutical nanocarriers with improved solubilization efficiency and comparable stability to spherical micelles, as well as better safety and efficacy in vitro compared to the prevalent Cremophor EL TAX formulation.
在此由相同的两亲性二嵌段共聚物聚（环氧乙烷）-b-聚（ε-己内酯）（PEO [5 kDa]-PCL [6.5 kDa]）制备蠕虫状和球形胶束，以比较疏水性药物的负载和递送情况。
这种可降解共聚物的蠕虫状胶束横截面为纳米级，能自发组装成微米级的稳定长度，在某些方面类似于丝状病毒，因此有了“丝状胶束”这一名称。高度灵活的蠕虫状胶束也可通过超声处理生成由相同共聚物组成的动力学稳定的球形胶束。
裂变过程利用了PCL核是流体而非玻璃态或结晶态这一发现，疏水性抗癌药物紫杉醇（TAX）的核负载表明，蠕虫状胶束负载和溶解的药物量是球形胶束的两倍。在与临床常用增溶剂聚氧乙烯蓖麻油（Cremophor EL）比较的细胞毒性试验中，两种胶束载体的毒性都小得多，两种负载TAX的胶束对A549人肺癌细胞的抗癌活性也都高出五倍。
基于PEO-PCL的蠕虫状丝状胶束似乎是很有前景的药物纳米载体，其增溶效率更高，与球形胶束稳定性相当，且与常用的聚氧乙烯蓖麻油TAX制剂相比，体外安全性和疗效更好。
