中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (12): 2166-2170.doi: 10.3969/j.issn.1673-8225.2011.12.019

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

负载As2O3壳聚糖纳米粒的药代动力学及其毒性观察

孙晋敏，夏正东，周士东，于德东，李琳琳，柳  红   

  1. 徐州医学院病理学教研室，江苏省徐州市  221002
  • 收稿日期:2010-09-20 修回日期:2010-11-01 出版日期:2011-03-19 发布日期:2011-03-19
  • 通讯作者: 柳红，教授，徐州医学院病理学教研室，江苏省徐州市 221002 hongliu04@yahoo.com
  • 作者简介:孙晋敏★，女，1982年生，山东省枣庄市人，汉族，南方医科大学毕业，硕士，助教，主要从事肿瘤的转移与抗转移研究。 sunjinmin198206@163.com 并列第一作者：夏正东，男，1980年生，江苏省建湖市人，汉族，徐州医学院毕业，硕士，医师，主要从事肿瘤病理学研究。

Pharmacokinetic and toxicity observation of arsenic trioxide-loaded chitosan nanoparticlest

Sun Jin-min, Xia Zheng-dong, Zhou Shi-dong, Yu De-dong, Li Lin-lin, Liu Hong   

  1. Department of Pathology, Xuzhou Medical College, Xuzhou   221002, Jiangsu Province, China
  • Received:2010-09-20 Revised:2010-11-01 Online:2011-03-19 Published:2011-03-19
  • Contact: Liu Hong, Professor, Department of Pathology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China hongliu04@yahoo.com
  • About author:Sun Jin-min★, Master, Assistant, Department of Pathology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China Xia Zheng-dong, Master, Physician, Department of Pathology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China Sun Jin-min and Xia Zheng-dong equally contributed to this work.

PDF

566

摘要：

背景：As2O3作为抗肿瘤药物具有不同程度的不良反应，目前尚没有可以较好降低As2O3不良反应的方法。
目的：观察负载As2O3壳聚糖纳米粒在体内是否有缓释作用，是否可以延长药物作用时间，减低As2O3毒副作用。
方法：将20只SD大鼠以抽签法随机分为As2O3组和壳聚糖纳米粒-As2O3组进行药代动力学测定，于给药前和给药后不同时间点测定血液中砷浓度；将40只SD大鼠随机分为壳聚糖纳米粒组、壳聚糖纳米粒- As2O3组、As2O3组、生理盐水组进行毒理学检测，检测血浆中谷丙转氨酶、谷草转氨酶、肌酸激酶、肌酐、尿素氮水平，并结合苏木精-伊红染色形态学观察心、肝、肾组织形态学变化。
结果与结论：壳聚糖纳米粒- As2O3组较As2O3组半衰期明显延长(P < 0.05)。除肌酸激酶外，As2O3组其他各指标均高于其他各组(P < 0.05)；而含相同浓度As2O3的壳聚糖纳米粒As2O3组与壳聚糖纳米粒组、生理盐水组各项指标差异无显著性意义(P > 0.05)。As2O3组大鼠肝脏和肾脏均有较明显的病理学改变，壳聚糖纳米粒- As2O3组未见明显形态学改变。4组大鼠心脏均未见明显形态学改变。说明负载As2O3壳聚糖纳米粒在体内有缓释作用，可以延长药物作用时间，减轻As2O3的毒副作用。

关键词: 壳聚糖纳米粒, As2O3, 负载As2O3壳聚糖纳米粒, 药代动力学, 药物毒理学

Abstract:

BACKGROUND: Arsenic trioxide (As2O3) as an anticancer drug has obvious side-effect, however, no good method has been found to reduce As2O3 side effects.
OBJECTIVE: To assay whether As2O3 loaded chitosan nanoparticles (NPCS-As2O3) could delay releasing time, could prolong As2O3 duration time and reduce As2O3 drug side-effect.
METHODS: Twenty SD rats were evenly divided into As2O3 group and NPCS-As2O3 group for pharmacokinetics determination, the blood concentrations of arsenic were detected before and after the medicine treatment at different time points. For drug toxicology assay, 40 SD rats were evenly divided into four groups, namely As2O3 group, NPCS-As2O3 group, NPCS group and normal sodium group. The alanine aminotransferase, aspertate aminotransferase, creatine kinase, creatinine, urea nitrogen level in plasma were tested. The heart, liver, kidney toxicity of NPCS-As2O3 was observed through morphological observation of hematoxylin-eosin staining.
RESULTS AND CONCLUSION: NPCS-As2O3 significantly prolonged the half-life compared with the As2O3 (P < 0.05). Except for creatine kinase, plasma biochemical indicators of As2O3 group were statistically significant higher than any other group (P < 0.05). There was no statistically significance between plasma biochemical indicators of NPCS-As2O3 group with the same As2O3 plasma concentration and NPCS group and normal sodium group (P > 0.05). The liver and kidney showed obvious pathological changes in As2O3 group, while no morphology change was seen in NPCS-As2O3 group. In the four groups, the hearts all had no distinct morphological change. NPCS-As2O3 has delayed the drug release, prolonged the drug effective time and reduced the toxicity of As2O3 in vivo.

中图分类号: