Study on in vivo distribution of liver-targeting nanopaticles encapsulating thymidine kinase gene (TK gene) in mice

Study on in vivo distribution of liver-targeting nanopaticles encapsulating thymidine kinase gene (TK gene) in mice
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包裹胸苷激酶基因(TK基因)的肝脏靶向纳米颗粒在小鼠体内分布的研究

DOI:
10.1007/s10856-007-3182-7
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发表时间:
2008-02
影响因子:
3.7
通讯作者:
Liu, Ji
Liu, Ji
中科院分区:
工程技术3区
文献类型:
--
作者:
Zhang, Zhi Rong;He, Qin;Yuan, Wen Min;Liu, Ji

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通过双乳液蒸发技术制备由负载新的重组质粒pEGFP-TKAFB(TK-PLGA-NPs)的聚乳酸-共-乙醇酸(PLGA)聚合物配制的纳米粒。采用溴化乙锭(EB)染色法和γ-射线衍射法研究了粒径为50 ~ 100 nm的TK-PLGA-NPs的体外和体内释药行为。结果表明,TK-PLGA-NPs中DNA(pEGFP-TKAFB质粒)的体外释放速率符合Higuichi方程,并与PLGA聚合物的分子量有关。0.5小鼠尾静脉注射32 P标记的pEGFP-TKAFB质粒(32 P-TK-PLGA-NP)纳米粒后h,肝脏放射性强度占总放射性强度的70%以上,是注射32 P标记的pEGFP-TKAFB质粒(32 pEGFP-TKAFB质粒,32 P-TK)的1.4倍。同样,小鼠皮下注射32 P-TK-PLGA-NPs后2 h,肝脏中的放射性占总放射性的比例超过70%,是裸32 P-TK的1.6倍。这些数据表明TK-PLGA-NPs具有肝靶向和延迟药物释放的潜力。
Nanoparticles formulated from polylactic-co-glycolic acid (PLGA) polymer loading a new recombinant plasmid pEGFP-TKAFB (TK-PLGA-NPs) were prepared by a double-emulsion evaporation technique. Both in vitro and in vivo release behaviors of TK-PLGA-NPs (with particle diameter ranged from 50 to 100 nm) were investigated, using ethidium bromide (EB) staining and gamma scintigraphy, respectively. The results indicated that the in vitro release rate of DNA (pEGFP-TKAFB plasmid) in TK-PLGA-NPs showed good fit into the Higuichi Equation and dependence in the molecular weight of PLGA polymer. 0.5 h after injection of nanoparticles containing32P labeled pEGFP-TKAFB plasmid (32P-TK-PLGA-NP) via caudal vein of the mice, the ratio of radioactivity intensity in the liver to total intensity was above 70%, which showed a 1.4-fold increase over that by injection of32P labeled pEGFP-TKAFB plasmid (32pEGFP-TKAFB plasmid,32P-TK). Similarly, 2 h after hypodermic injection of32P-TK-PLGA-NPs in mice, the ratio of radioactivity in the liver against total radioactivity was more than 70%, which was 1.6-fold compared with naked32P-TK. All these data showed that the TK-PLGA-NPs has the potential for liver-targeting and delayed drug release.
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