Paclitaxel nanosuspensions for targeted chemotherapy - nanosuspension preparation, characterization, and use
Paclitaxel nanosuspensions for targeted chemotherapy - nanosuspension preparation, characterization, and use
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DOI：
10.3109/10837450.2013.789911
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发表时间：
2014-06-01
影响因子：
3.4
通讯作者：
Hoffman, Robert M.
中科院分区：
文献类型：
--
作者：
Lee, Sarah E.;Bairstow, Shawn F.;Hoffman, Robert M.
目的：制备一种稳定的紫杉醇纳米混悬液，并考察其作为靶向化疗药物的应用前景。采用不同的颗粒涂层来评估其对体外细胞摄取的影响。然后进行体内工作以证明在荷瘤小鼠模型中的有效性。材料和方法：采用均质法制备紫杉醇纳米混悬液，并包被赋形剂。表面电荷用zeta电位测定，效价用高效液相色谱测定，溶解度用紫外探针测定。通过流式细胞术进行细胞摄取研究。通过体内实验测定紫杉醇纳米混悬液（paclitaxel - ns）的停留时间、最大耐受剂量和疗效。结果：制备了稳定的紫杉醇纳米混悬液，并包被多种辅料。小鼠研究表明，纳米混悬液在头颈癌模型和卵巢癌模型中具有良好的耐受性，在延长小鼠生存方面至少与静脉注射紫杉醇对照组一样有效，且总给药剂量低于传统的静脉给药途径。结论：紫杉醇纳米混悬液适合细胞摄取。纳米混悬液通过两种不同的给药途径有效延长了两种不同的异种移植原位小鼠癌症模型的寿命。
Objective: The purpose of this work was to prepare a stable paclitaxel nanosuspension and test it for potential use as a targeted chemotherapeutic. Different particle coatings were employed to assess their impact on cellular uptake in vitro. In vivo work was then performed to demonstrate efficacy in tumor-bearing mouse models.Materials and method: Paclitaxel nanosuspensions were prepared using a homogenization process and coated with excipients. Surface charge was measured by zeta potential, potency by high-performance liquid chromatography, and solubility using an in-line UV probe. Cellular uptake studies were performed via flow cytometry. In vivo experiments were performed to determine residence time, maximum tolerated dose, and the efficacy of paclitaxel nanosuspensions (Paclitaxel-NS).Results: A stable paclitaxel nanosuspension was prepared and coated with various excipients. Studies in mice showed that the nanosuspension was well-tolerated and at least as effective as the IV Taxol control in prolonging mouse survival in a head and neck cancer model as well as an ovarian cancer model with a lower overall drug dose than the traditional IV administration route.Conclusions: The paclitaxel nanosuspension is suitable for cellular uptake. The nanosuspension was effective in prolonging life in two separate xenograft orthotopic murine cancer models through two separate routes of administration.