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聚乙二醇化壳聚糖纳米粒增强了奥曲肽在乳腺癌治疗中的再利用。

PEGylated chitosan nanoparticles potentiate repurposing of ormeloxifene in breast cancer therapy.

机构信息

Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.

Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, UP, India.

出版信息

Nanomedicine (Lond). 2016 Aug;11(16):2147-69. doi: 10.2217/nnm-2016-0095. Epub 2016 Jul 27.

DOI:10.2217/nnm-2016-0095
PMID:27463533
Abstract

AIM

Development and optimization of ormeloxifene-loaded PEGylated chitosan nanoparticles (CNPs) for enhancing its literature profound therapeutic activity against breast cancer.

METHODS

CNPs were prepared by ionotropic gelation method and characterized.

RESULTS

Optimized formulation (CNPs10) had average 304 nm particle size with 0.247 polydispersity index and spherical shape with +31 mV surface charge. CNPs10 had 88.37% entrapment efficiency and 20.93% loading efficiency. CNPs10 demonstrated dose-dependent enhancement in cytotoxicity, cellular uptake, apoptosis, disruption of mitochondrial membrane potential and activation of caspase-3 in breast cancer MDA-MB-231 and MCF-7 cells over free ormeloxifene. In vivo studies divulged improved pharmacokinetic parameters, reduced toxicity, suppressed tumor burden and increased survival in CNPs10-treated female Sprague-Dawley rats.

CONCLUSION

PEGylated CNPs enhanced anticancer activity of ormeloxifene.

摘要

目的

研制并优化载奥洛昔芬的聚乙二醇化壳聚糖纳米粒(CNPs),以增强其对乳腺癌的文献报道的治疗活性。

方法

采用离子凝胶法制备 CNPs,并对其进行了表征。

结果

优化的配方(CNPs10)具有平均 304nm 的粒径、0.247 的多分散指数和球形形状,表面带正电荷 +31mV。CNPs10 的包封效率为 88.37%,载药效率为 20.93%。CNPs10 在体外对乳腺癌 MDA-MB-231 和 MCF-7 细胞的细胞毒性、细胞摄取、细胞凋亡、线粒体膜电位破坏和 caspase-3 激活具有剂量依赖性增强作用,优于游离奥洛昔芬。体内研究表明,CNPs10 可改善药代动力学参数,降低毒性,抑制肿瘤负担,提高荷瘤雌性 Sprague-Dawley 大鼠的存活率。

结论

聚乙二醇化 CNPs 增强了奥洛昔芬的抗癌活性。

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