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Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems.
Cancer Nanotechnology ( IF 4.5 ) Pub Date : 2014-06-18 , DOI: 10.1186/s12645-014-0003-9
Dipti Kakkar Thukral 1 , Shweta Dumoga 1 , Shelly Arora 1 , Krishna Chuttani 1 , Anil K Mishra 1
Affiliation  

In this work matrix based nanoparticulate polymer systems have been designed using the diacrylate derivative of the well-known biocompatible polymer, poly(ethylene glycol) (PEG). This has been crosslinked using bifunctional (ethyleneglycol dimethacrylate) and tetrafunctional (pentaerythritol tetraacrylate) crosslinkers in varied concentrations (10-90%) to result in a polymeric network. The crosslinked polymers thus obtained were characterized by spectroscopic techniques (NMR and FTIR) and then prepared nanoparticles by the nanoprecipitation technique. Particle size analysis showed sizes of ~150 nm (PDI < 1) (with tetrafunctional crosslinker) and ~300 nm (with bifunctional crosslinker). Both the systems however showed unimodal narrow particle size distributions with negative zeta potential values of -15.6 and -7.3 respectively. Cytotoxicity of these formulations was evaluated by MTT assay showing non-cytotoxic nature of these carrier systems. In vitro drug loading and release studies were carried out using a model chemotherapeutic drug, methotrexate(MTX). These MTX loaded nanoformulations have also been evaluated biologically with the help of in vivo studies using radiolabeling techniques (with 99mTc radionuclide). The blood kinetics profile of the formulations was studied on New Zealand Albino rabbits while the biodistribution studies were performed on balb/c mice (with EAT tumours), which revealed a hepatobiliary mode of elimination. These preliminary studies clearly demonstrated the ability of these multifunctional crosslinkers to result in tight nanosized networks with biocompatible polymers such as PEG and their potential to carry chemotherapeutic drugs.

中文翻译:


化疗药物的潜在载体:基于基质的纳米颗粒聚合物系统。



在这项工作中,使用众所周知的生物相容性聚合物聚乙二醇(PEG)的二丙烯酸酯衍生物设计了基于基质的纳米颗粒聚合物系统。使用不同浓度(10-90%)的双官能(乙二醇二甲基丙烯酸酯)和四官能(季戊四醇四丙烯酸酯)交联剂进行交联,形成聚合物网络。通过光谱技术(NMR 和 FTIR)对由此获得的交联聚合物进行表征,然后通过纳米沉淀技术制备纳米颗粒。粒度分析显示尺寸约为 150 nm (PDI < 1)(使用四功能交联剂)和 ~300 nm(使用双功能交联剂)。然而,这两个系统都显示出单峰窄粒径分布,负 zeta 电位值分别为 -15.6 和 -7.3。通过 MTT 测定评估这些制剂的细胞毒性,显示这些载体系统的非细胞毒性性质。使用模型化疗药物甲氨蝶呤(MTX)进行体外药物装载和释放研究。这些载有 MTX 的纳米制剂还借助放射性标记技术(使用 99mTc 放射性核素)进行体内研究进行了生物学评估。在新西兰白化兔上研究了制剂的血液动力学特征,同时在 balb/c 小鼠(患有 EAT 肿瘤)上进行了生物分布研究,结果揭示了肝胆消除模式。这些初步研究清楚地证明了这些多功能交联剂能够与生物相容性聚合物(如 PEG)形成紧密的纳米级网络,以及它们携带化疗药物的潜力。
更新日期:2014-06-18
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