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紫杉醇包封于普朗尼克聚合物胶束在皮下和肺转移瘤小鼠模型中治疗黑色素瘤的潜力。

The potential of Pluronic polymeric micelles encapsulated with paclitaxel for the treatment of melanoma using subcutaneous and pulmonary metastatic mice models.

机构信息

School of Pharmacy, Fudan University, Shanghai, China.

出版信息

Biomaterials. 2011 Sep;32(25):5934-44. doi: 10.1016/j.biomaterials.2011.04.075. Epub 2011 May 18.

Abstract

The increasing global incidence of malignant melanoma combined with the poor prognosis and low survival rates of patients necessitates the development of new chemotherapeutic strategies. Thus, the objective of this present study was to investigate the therapeutic efficacy of Pluronic polymeric micelles encapsulating paclitaxel (PTX) in both B16F10 melanoma subcutaneous mice model and pulmonary metastatic mice model. Herein, we developed a PTX-loaded polymeric micelles (PF-PTX) consisting of Pluronic P 123 and F127 block copolymers with small particle size (∼25 nm), high encapsulation efficiency (>90%), good stability in lyophilized form and pH-dependent in vitro release. Furthermore, influence of PF-PTX on in vitro cytotoxicity was determined by MTT assay using B16F10 melanoma cell line, while cellular distribution of PF-PTX was detected by confocal microscopy. Additionally, C57BL/6 mice bearing subcutaneous or pulmonary B16F10 melanoma tumors were treated with Taxol or PF-PTX, and antitumor effect was compared. It was found that antitumor efficacy of PF-PTX in both tumor models showed significant tumor growth delay and increased survival. In summary, the simple Pluronic-based nanocarrier could be harnessed for the delivery of anticancer drug to melanoma, with increased therapeutic index.

摘要

恶性黑色素瘤的全球发病率不断上升,加上患者的预后不良和生存率低,这就需要开发新的化疗策略。因此,本研究的目的是研究紫杉醇(PTX)包载于聚轮烷胶束(PF-PTX)在 B16F10 黑色素瘤皮下小鼠模型和肺转移小鼠模型中的治疗效果。在这里,我们开发了一种由 Pluronic P 123 和 F127 两亲嵌段共聚物组成的载紫杉醇的聚合物胶束(PF-PTX),其具有较小的粒径(约 25nm)、高包封效率(>90%)、冻干形式下的良好稳定性以及 pH 依赖性体外释放。此外,通过 MTT 测定法用 B16F10 黑色素瘤细胞系测定了 PF-PTX 对体外细胞毒性的影响,并用共聚焦显微镜检测了 PF-PTX 的细胞分布。此外,用 Taxol 或 PF-PTX 治疗携带皮下或肺 B16F10 黑色素瘤肿瘤的 C57BL/6 小鼠,并比较了抗肿瘤效果。结果发现,PF-PTX 在两种肿瘤模型中的抗肿瘤效果均表现出显著的肿瘤生长延迟和生存率提高。总之,这种简单的基于聚轮烷的纳米载体可以用于将抗癌药物递送至黑色素瘤,提高治疗指数。

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