一个用于治疗癌症的紫杉醇聚合物共轭的理化性能及生物相容性

2012-03-28 13:58 来源:丁香园 作者:上海华东师范大学生命医学研究所
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Int J Nanomedicine 2011 ;6 2557-66. [IF:4.976]
Physicochemical properties and biocompatibility of a polymer-paclitaxel conjugate for cancer treatment.
Yang D , Van S , Liu J , Wang J , Jiang X , Wang Y , Yu L .
Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, China.
上海华东师范大学生命医学研究所,上海跨学科课程研究所

Abstract
Poly(L-γ-glutamylglutamine) paclitaxel (PGG-PTX) conjugate is a non-diblock polymeric drug nanoparticle intended to improve the therapeutic index of paclitaxel. The purpose of the present study was to elucidate further the physicochemical properties of PGG-PTX in order to proceed with its clinical development. PGG-PTX was designed by integration of a hydrophobic paclitaxel conjugate through an added hydrophilic glutamic acid onto poly(L-glutamic acid). The addition of a flexible glutamic linker between PGA and paclitaxel resulted in spontaneous self-assembly of a PGG-PTX conjugate into nanoparticles. The PGG-PTX conjugate was stable as a lyophilized solid form. An in vitro viability experiment showed that PGG-PTX was effective after a longer incubation period, the same trend as Taxol. In vitro studies using NCI-H460 and B16F0 cancer cells demonstrated significantly high cellular uptake after 30 minutes of incubation. The in vivo biocompatibility of PGG-PTX conjugate was evaluated in the NCI-H460 tumor model, the assessment of tissue seemed to be normal after 21 days of treatment. These results are encouraging for further development of non-block polymeric paclitaxel nanoparticles for treatment of cancer.

摘要:
多聚(左旋γ谷酰基谷氨酰胺)紫杉醇缀合物(PGG-PTX)是一个为了提高紫杉醇治疗指数的纳米微粒级的非双嵌段聚合物药物。
现在研究的目的是为了推动PGG-PTX临床发展而进一步明确其物理化学性质。
PGG-PTX是用疏水性的紫杉醇缀合物通过在多聚左旋谷氨基酸端添加一个亲水性的谷氨基酸整合而成的。
PGA与紫杉醇之间添加的这个活动的谷氨酸链导致其自发地把一个PGG-PTX缀合物自行组装成纳米级微粒。
PGG-PTX缀合物在冻干的固体形态下是稳定的。一个体外生存实验表明PGG-PTX在一个长潜伏期后还可以起作用,这点与紫杉酚一样。
体外用NCI-H460和B16F0研究证明癌症细胞30分钟潜伏后显著的高细胞摄入。在NCI-H460肿瘤模型中活体内PGG-PTX缀合物的生物相容性进行了评估,在经过21天治疗后,被观察的组织看起来是变得正常了。
这些结果对非双嵌段多聚紫杉醇纳米微粒在癌症治疗中的进一步发展提供支持。

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