喜树碱纳米颗粒细胞毒性及免疫和亚急性毒性的评价

T. Hong, Lim Sm, Y. Huang, K. Shu, Liang Lx, L. Liu, Liu Zy
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引用次数: 2

摘要

具有聚乙二醇外壳的cpt负载NPs可以提高其在水中的溶解度并保持长时间的循环。本实验评价了CPT NPs的细胞毒性、免疫毒性和亚急性毒性。喜树碱(CPT)掺入生物素-F127-PLA或F127-PLA聚合物纳米颗粒中;非靶向CPT NPs采用透析法,靶向CPT NPs采用抗ca125抗体。同时对小鼠成纤维细胞样L-929细胞株进行了细胞毒性试验。两种cpt负载的NPs对免疫的影响也通过碳颗粒清除率测定来确定。每只小鼠腹腔注射0.4 ml/20 g.bw纳米颗粒,连续28天进行亚急性毒性试验。结果表明,CPT NPs降低了游离CPT对L-919细胞的毒性。CPT NPs对正常小鼠没有诱导吞噬作用。亚急性毒性研究结束时,CPT NP组与对照组在血液参数分析和主要脏器重量内脏系数方面均无差异。这些结果表明,新的CPT NPs可能在细胞和生物体水平上引起低毒性作用。
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Evaluation of the Cytotoxicity and Immune and Subacute Toxicity of Camptothecin-loaded Nanoparticles
CPT-loaded NPs with polyethylene glycol shells can increase its solubility in water and remain in circulation for a long time. This experiment has evaluated cytotoxicity and immune and subacute toxicity of CPT NPs. Camptothecin (CPT) was incorporated into biotin-F127-PLA or F127-PLA polymeric nanoparticles; a dialysis method was used for non-targeted CPT NPs and anti-CA125 antibodies for targeted CPT NPs. A cytotoxicity test was also conducted based on the growth inhibition of the mouse fibroblast-like L-929 cell line. The effects of the two CPT-loaded NPs on immunity were also determined through a carbon particle clearance rate assay. Each mouse was intraperitoneally injected with 0.4 ml/20 g.bw nanoparticles for 28 consecutive days in the subacute toxicity test. Results have showed that CPT NPs have reduced the toxicity of free CPT on the L-919 cells. The CPT NPs did not induce phagocytosis in the normal mice. At the end of subacute toxicity study no difference was found between the CPT NP and control groups in blood parameter analysis and main organ weight visceral coefficients. These results suggested that the new CPT NPs might elicit low toxic effects at cellular and organism levels.
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