一步法制备功能型层状双氢氧化物药物递送体系的最优化条件研究
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摘要
层状双氢氧化物LDH作为拥有特殊层状结构的纳米药物载体,具有低毒性、可降解性以及药物缓释的性能。因此,设计合成了具有可降解的低毒性靶向药物缓释系统LDH/HA-PEG/5-FU。为了使药物递送系统LDH/HA-PEG/5-FU获得最大载药量,采用控制变量法测定了在不同的反应时间、反应温度以及不同的HA-PEG投放浓度下LDH/HA-PEG/5-FU的药物包封率、zeta电位及粒径,最终得出一步法合成LDH/HA-PEG/5-FU的最优反应条件为,恒温水浴70℃,反应时间24 h,加入浓度为1 mg/mL的HA-PEG分散液,在上述条件下合成的药物递送体系LDH/HA-PEG/5-FU可获得最高载药量。
The layered double hydroxide LDH is one kind of nano drug carriers which have special layered structure, low toxicity, degradability and sustained drug release property. In our study, a low toxicity targeted drug release system LDH/HA-PEG/5-FU with fine degradability was synthesized. In order to obtain the maximum drug loading for the system LDH/HA-PEG/5-FU, the control variable method was used to detect the encapsulation efficiency, zeta potential and particle size of LDH/HA-PEG/5-FU at different reaction times, different reaction temperatures and different concentrations of HA-PEG. Finally, the optimal reaction condition for one-method synthesis of LDH/HA-PEG/5-FU was obtained: thermostatic waterbath of 70 ℃, 24 h of reaction time and 1 mg/mL of the concentration of HA-PEG. The drug delivery system of LDH/HA-PEG/5-FU synthesized under the above conditions was able to obtain the maximum drug loading.
The layered double hydroxide LDH is one kind of nano drug carriers which have special layered structure, low toxicity, degradability and sustained drug release property. In our study, a low toxicity targeted drug release system LDH/HA-PEG/5-FU with fine degradability was synthesized. In order to obtain the maximum drug loading for the system LDH/HA-PEG/5-FU, the control variable method was used to detect the encapsulation efficiency, zeta potential and particle size of LDH/HA-PEG/5-FU at different reaction times, different reaction temperatures and different concentrations of HA-PEG. Finally, the optimal reaction condition for one-method synthesis of LDH/HA-PEG/5-FU was obtained: thermostatic waterbath of 70 ℃, 24 h of reaction time and 1 mg/mL of the concentration of HA-PEG. The drug delivery system of LDH/HA-PEG/5-FU synthesized under the above conditions was able to obtain the maximum drug loading.
引文
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[3] Li B X,He J,Evans D G,et al.Inorganic layered double hydroxides as a drug delivery system—intercalation and in vitro release of fenbufen[J].Applied Clay Science,2004,27(3/4):199-207.
[4] Choy J H,Jung J S,Oh J M,et al.Layered double hydroxide as an efficient drug reservoir for folate derivatives[J].Biomaterials,2004,25(15):3059-3064.
[5] Francesca B,Alistella A,Morena N,et al.Intercalation of 5-fluorouracil into ZnAl hydrotalcite-like nanoparticles:preparation,characterization and drug release[J].Applied Clay Science,2014,101:320-326.
[6] Li L,Wenyi G,Che J Z,et al.Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles[J].Biomaterials,2014,35(10):3331-3339.
[7] Katharina L,Marcus N,Xu Z P.Efficient siRNA delivery to mammalian cells using layered double hydroxide nanoparticles[J].Biomaterials,2010,31:1821-1829.
[8] Jiang Z L,Dong B,Chen B T,et al.Multifunctional Au@mSiO2/rhodamine B isothiocyanate nanocomposites:cell imaging,photocontrolled drug release and photothermal threapy for cancer cells[J].Small,2013,9(4):604-612.
[9] Xi Lijuan,Liu Ying,Lv Hongbin.Preparation of layered double hydroxide and its application in treatment of anionic contaminants[J].Silicate,2013,32(8):1567-1572 (in Chinese).郗丽娟,刘莹,吕洪滨.层状双金属氢氧化物的制备及其在处理阴离子污染物方面的应用[J].硅酸盐学报,2013,32(8):1567-1572.
[10] Sheng T,Guo H C,Yuepeng C,et al.Automated dispersive solid-phase extraction using dissolvable Fe3O4-layered double hydroxide core-shell microspheres as sorbent[J].Analytical Chemistry,2014,86(22):11070-11076.
[11] Stoica G,Serrano I C,Figuerola A ,et al.Layered double hydroxides as carriers for quantum dots@silica nanospheres [J].Nanoscale,2012,4(17):5409-5419.
[12] Serrano I C,Stoica G,Palomares,E .Increasing cell viability using Cd-free-InP/ZnS@silica@layered double hydroxide-materials for biological labeling [J].RSC Advances,2016,6(37):31210-31213.
[13] Zhang M L,Yao Q F,Lu C,et al.Layered double hydroxide-carbon dot composite:high-performance adsorbent for removal of anionic organic dye[J].ACS Applied Materials & Interfaces,2014,(6):20225- 20233.
[14] Lu Ailian,Hu Zhongai,Hu Yingyin,et al,Preparation and electrochemical capacitance behavior of reduced graphene oxide/Al-Ni layered double hydroxide complex[J].New Chemical Materials,2012,40(12):100-103(in Chinese).鲁爱莲,胡中爱,胡英瑛,等.还原氧化石墨烯 /Al-Ni 层状双氢氧化物复合物的制备及其电化学电容行为[J].化工新型材料,2012,40(12):100-103.
[15] Anjie D,Xue L,Liandong D,et al.Layered double hydroxide modified by PEGylated hyaluronic acid as a hybrid nanocarrier for targeted drug delivery[J].Transactions of Tianjin University,2016,22:237-246.
[16] Zhang W,Cheng Q,Guo S,et al.Gene transfection efficacy and biocompatibility of polycation/DNA complexes coated with enzyme degradable PEGylated hyaluronic acid[J].Biomaterials,2013,34(27):6495-6503.