Micelles of different morphologies - Advantages of worm-like filomicelles of PEO-PCL in paclitaxel delivery
Micelles of different morphologies - Advantages of worm-like filomicelles of PEO-PCL in paclitaxel delivery
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DOI：
10.1007/s11095-007-9335-z
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发表时间：
2007-11-01
影响因子：
3.7
通讯作者：
Discher, Dennis E.
中科院分区：
文献类型：
--
作者：
Cai, Shenshen;Vijayan, Kandaswamy;Discher, Dennis E.
蠕虫状和球形胶束均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，以比较疏水性药物的负载和递送。这种可降解共聚物的蠕虫状胶束的横截面为纳米级，并自发组装成稳定的微米长度，类似于丝状病毒在某些方面，因此建议使用“filomicelles”这个绰号。高度灵活的蠕虫状胶束也可以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 核心是流体而不是玻璃状或晶体的发现，并且疏水性抗癌药物输送紫杉醇 (TAX) 的核心负载表明，蠕虫状胶束负载和溶解的药物是球形胶束的两倍。在细胞毒性测试中，与临床流行的增溶剂 Cremophor (R) EL 相比，两种胶束载体的毒性要低得多，并且两种类型的 TAX 负载胶束对 A549 人肺癌细胞的抗癌活性也高出五倍。基于 PEO-PCL 的蠕虫状丝状胶束似乎是有前途的药物纳米载体，具有更高的增溶效率和与球形胶束相当的稳定性，以及更好的安全性和有效性与流行的 Cremophor (R) EL TAX 配方进行体外比较。
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 (R) 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 (R) EL TAX formulation.