Supra-molecular Assembly Characterization and Urgent Toxic Level of "Dextran-Magnetic Layered Double Hydroxide-Fluorouracil" Drug Delivery System

doi:10.6023/A1105183

Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (02): 161-169.DOI: 10.6023/A1105183 Previous Articles Next Articles

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“右旋糖酐-磁性层状复合氢氧化物-氟尿嘧啶”给药系统的超分子组装表征与急毒性水平

苟国敬^a,b, 王志宇^a, 刘彦红^a,b, 薛冰^a,b, 黄洁^a,b, 孙岳^a,b

a 宁夏医科大学医用化学系银川 750004;
b 宁夏医科大学医学科学技术研究中心银川 750004

投稿日期:2011-05-18 修回日期:2011-09-28 发布日期:2012-02-25
通讯作者: 苟国敬 E-mail:ggj64@yahoo.com.cn
基金资助:
国家自然科学基金(No.20961008);宁夏高等学校科学技术研究重点项目基金(No.200919341);宁夏自然科学基金(No.NZ09102);教育部科学技术研究重点项目基金(No.207127)资助项目.

Supra-molecular Assembly Characterization and Urgent Toxic Level of "Dextran-Magnetic Layered Double Hydroxide-Fluorouracil" Drug Delivery System

Gou Guojing^a,b, Wang Zhiyu^a, Liu Yanhong^a,b, Xue Bing^a,b, Huang Jie^a,b, Sun Yue^a,b

a Department of Chemistry, Ningxia Medical University, Yinchuan 750004;
b Research Center of Medical Science and Technology, Ningxia Medical University, Yinchuan 750004

Received:2011-05-18 Revised:2011-09-28 Published:2012-02-25
Supported by:
Project supported by the National Natural Science Foundation of China (No.20961008);Ningxia Higher School Science and Technology Research Key Project Fund (No.200919341);Ningxia Natural Science Fund (No.NZ09102);Ministry of Education Science and Technology Research Key Project Fund (No.207127).

The drug delivery system DMF with a formation of DET-MLDH-FU (dextran-magnetic layered double hydroxide-fluorouracil) was synthesized by the “precursor co-precipitation-intercalated assembly with ion exchange-dextran in situ composite-solvent conversion” technology, the crystal-phase characteristic and slow-release performance of DMF system were investigated through XRD, IR, TEM, TG characterization and dissolve out experiment in vitro. The urgent toxic levels of DMF and MLDH were inspected through mice animal experiments of irrigation stomach and intraperitoneal injection. The results showed that the XRD of DMF, MLDH-FU and MLDH matched with R-sixtetragonum LDH series, mixed by Fe_3.6Fe_0.9(O,OH,Cl)₉ type crystal-phase and trace iron oxide. The DMF supra-molecular system consisted by DET, MLDH and FU components had a core-shell structure formed through grading assembly. The drug release model of DMF accorded with the zero-order kinetics equation C-1.162×10^-5=4.566×10^-7t at pH 7.35 of PBS in vitro, and its rate constant was 4.566×10^-7 mol^-1·L·m^-1. DMF, MLDH-FU and MLDH could be excreted in vivo through normal metabolism, with a tiny oral toxicity. The LD₅₀ of intraperitoneal injection experiment were 2542.8 mg·kg^-1 and 1951.0 mg·kg^-1 respectively for DMF and MLDH-FU, which meant all belonged to low toxic substances. Composite assembly with DET produced the antioxidant protection function for the layered structure of MLDH-FU, resulting in selection, separation and encapsulation of different particles, and gave rise to improving for the slow-release effect of MLDH-FU, strengthening of controlled-release characteristic for MLDH, and reducing of the urgent toxic levels for DMF drug delivery system.

Key words: dextran-magnetic layered double hydroxide-fluorouracil (DET-MLDH-FU) drug delivery system, three-level supra-molecular assembly, the drug release model, urgent toxic level

Cite this article

Gou Guojing, Wang Zhiyu, Liu Yanhong, Xue Bing, Huang Jie, Sun Yue. Supra-molecular Assembly Characterization and Urgent Toxic Level of "Dextran-Magnetic Layered Double Hydroxide-Fluorouracil" Drug Delivery System[J]. Acta Chimica Sinica, 2012, 70(02): 161-169.

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“右旋糖酐-磁性层状复合氢氧化物-氟尿嘧啶”给药系统的超分子组装表征与急毒性水平

Supra-molecular Assembly Characterization and Urgent Toxic Level of "Dextran-Magnetic Layered Double Hydroxide-Fluorouracil" Drug Delivery System

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