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载多柔比星的聚(N,N-二乙基丙烯酰胺)/功能化石墨烯量子点水凝胶作为纳米药物载体用于治疗小鼠转移性肺癌。

Poly(N,N-diethyl acrylamide)/functionalized graphene quantum dots hydrogels loaded with doxorubicin as a nano-drug carrier for metastatic lung cancer in mice.

机构信息

Department of Chemical Engineering, National Institute of Technology Karnataka, Surathkal, Mangalore, Karnataka, India.

Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Dec;105:110094. doi: 10.1016/j.msec.2019.110094. Epub 2019 Aug 19.

DOI:10.1016/j.msec.2019.110094
PMID:31546441
Abstract

Cancer has emanated as a daunting menace to human-kind even though medicine, science, and technology has reached its zenith. Subsequent scarcity in the revelation of new drugs, the exigency of salvaging formerly discovered toxic drugs such as doxorubicin has emerged. The invention of drug carrier has made drug delivery imminent which is ascribable to its characteristic traits of specific targeting, effective response to stimuli and biocompatibility. In this paper, the nanoscale polymeric drug carrier poly(N,N-diethyl acrylamide) nanohydrogel has been synthesized by inverse emulsion polymerization. Lower critical solution temperature of the polymeric carrier has been modified using graphene quantum. The particle size of pure nanohydrogel was in the range of 47 to 59.5 nm, and graphene quantum dots incorporated nanohydrogels was in the range of 68.1 to 87.5 nm. Doxorubicin (hydroxyl derivative of anthracycline) release behavior as a function of time and temperature was analyzed, and the Lower critical solution temperature of the synthesized nanohydrogels has been found to be in the range of 28-42 °C. Doxorubicin release characteristics have improved significantly as the surrounding temperature of the release media was increased near to physiological temperature. Further, the cumulative release profile was fitted in the different kinetic model and found to follow a Fickian diffusion release mechanism. The hydrogel was assessed for its cytotoxicity in B16F10 cells by MTT assay. In-vivo studies were done to study the lung metastasis by melanoma cancer and the results showed a rational favorable prognosis which was confirmed by evaluating hematological parameters and the non-immunogenic nature of nanohydrogel by cytokine assay. Comprehensively, the results suggested that poly(N,N-diethyl acrylamide) nanohydrogels have potential application as an intelligent drug carrier for melanoma cancer.

摘要

癌症已经成为人类的一大威胁,尽管医学、科学和技术已经达到了顶峰。随后,新药物的发现变得稀缺,因此需要挖掘以前发现的毒药物,如阿霉素。药物载体的发明使得药物输送成为可能,这归因于其特异性靶向、对刺激的有效反应和生物相容性等特点。在本文中,通过反相乳液聚合合成了纳米级聚合物药物载体聚(N,N-二乙基丙烯酰胺)纳米水凝胶。使用石墨烯量子点修饰了聚合物载体的低临界溶液温度。纯纳米水凝胶的粒径范围为 47 至 59.5nm,而掺入石墨烯量子点的纳米水凝胶的粒径范围为 68.1 至 87.5nm。分析了作为时间和温度函数的阿霉素(蒽环类药物的羟基衍生物)释放行为,并且发现合成纳米水凝胶的低临界溶液温度在 28-42°C 范围内。随着释放介质周围温度接近生理温度,阿霉素的释放特性得到了显著改善。此外,累积释放曲线拟合在不同的动力学模型中,发现遵循菲克扩散释放机制。通过 MTT 测定法评估了水凝胶在 B16F10 细胞中的细胞毒性。进行了体内研究以研究黑色素瘤癌症的肺转移,结果显示出合理的有利预后,通过评估血液学参数和细胞因子测定法评估纳米水凝胶的非免疫原性来证实了这一点。综上所述,结果表明聚(N,N-二乙基丙烯酰胺)纳米水凝胶作为黑色素瘤癌症的智能药物载体具有潜在的应用前景。

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