Zahr Alisar S, Pishko Michael V
Departments of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Biomacromolecules. 2007 Jun;8(6):2004-10. doi: 10.1021/bm070177m. Epub 2007 May 19.
An electrostatic layer-by-layer self-assembly technique was used to encapsulate solid core paclitaxel nanoparticles within a polymeric nanometer-scale shell. This approach provides a new strategy for the development of polymeric vehicles that control drug release and target diseased tissues and cells specific to the ailment, such as breast cancer. Core paclitaxel nanoparticles, 153 +/- 28 nm in diameter, were prepared using a modified nanoprecipitation technique. A nanoshell composed of multilayered polyelectrolytes, poly(allylamine hydrochloride) and poly(styrene-4-sulfonate) was assembled stepwise onto core charged drug nanoparticles. In vitro studies were performed to determine the anticancer activity of paclitaxel core-shell nanoparticles. Paclitaxel core-shell nanoparticles induced cell cycle arrest in the G2/M phase after 24 and 48 h of incubation with a human breast carcinoma cell line, MCF-7. Changes in MCF-7 cell morphology, fragmentation of the nucleus, and loss of cell-cell contacts indicated that the cells responded to paclitaxel core nanoparticles upon treatment for 24 and 48 h. Cells arrested in G2/M phase illustrated abnormal microtubule and actin cytoskeleton morphology. The core-shell drug nanoparticles fabricated using this procedure provide a new approach in the delivery of paclitaxel devoid of Cremophor EL, a solvent that causes adverse side effects in patients undergoing chemotherapy for treatment of metastasized mammary cancers.
采用静电层层自组装技术将固体核心紫杉醇纳米颗粒包裹在聚合物纳米级外壳中。这种方法为开发聚合物载体提供了一种新策略，该载体可控制药物释放并靶向特定疾病（如乳腺癌）的患病组织和细胞。使用改良的纳米沉淀技术制备了直径为153±28 nm的核心紫杉醇纳米颗粒。由多层聚电解质聚（烯丙胺盐酸盐）和聚（苯乙烯-4-磺酸盐）组成的纳米壳逐步组装到带电荷的核心药物纳米颗粒上。进行了体外研究以确定紫杉醇核壳纳米颗粒的抗癌活性。在用人类乳腺癌细胞系MCF-7孵育24小时和48小时后，紫杉醇核壳纳米颗粒诱导细胞周期停滞在G2/M期。MCF-7细胞形态的变化、细胞核的碎片化以及细胞间接触的丧失表明，在处理24小时和48小时后，细胞对紫杉醇核心纳米颗粒有反应。停滞在G2/M期的细胞显示出异常的微管和肌动蛋白细胞骨架形态。使用该程序制备的核壳药物纳米颗粒为紫杉醇的递送提供了一种新方法，该方法不含聚氧乙烯蓖麻油EL，聚氧乙烯蓖麻油EL是一种在转移性乳腺癌化疗患者中会引起不良副作用的溶剂。
