氧化石墨烯对多烯紫杉醇的高效装载和缓释性能及其经皮给药的渗透性研究
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摘要
目的合成新型的功能性氧化石墨烯-β-环糊精/多烯紫杉醇包合物(GO-DEX-β-CD/DOC)和四氧化三铁/氧化石墨烯-萘磺酸钠/多烯紫杉醇包合物(Fe_3O_4/GO-Na/DOC),并研究其对多烯紫杉醇(docetaxel,DOC)的装载、释放和经皮给药的渗透性能。方法以HPLC法测定DOC含量,并对制剂的高效装载和缓释性能进行研究,以离心法测定GO-DEX-β-CD/DOC和Fe_3O_4/GO-Na/DOC的包封率及载药率。将含药载体应用于离体和在体雌鼠皮肤,研究GO-DEX-β-CD/DOC和Fe_3O_4/GO-Na/DOC经雌鼠皮肤给药的渗透性。结果 Fe_3O_4/GO-Na/DOC的包封率和载药率更高,其释放具有较好的缓释性,经皮给药的渗透性能更好。结果显示,应用Fe_3O_4/GO-Na/DOC后90 h累积渗透量是(22.512±0.715)μg,15 min时皮肤内DOC浓度达峰值。给药5h后,雌鼠血液中检测出DOC质量浓度达到(76.886±1.232)μg/mL。结论 Fe_3O_4/GO-Na/DOC制备工艺可行,其缓释性及透皮效果更好,具有广阔应用前景。
Objective To synthetize the new-type GO-DEX-β-CD/DOC and Fe_3O_4/GO-Na/DOC inclusion compound, and study its high-efficiency loading, sustained-release and permeability as transdermal delivery for docetaxel(DOC) composites. Methods The concentration of DOC was determined by high efficiency liquid chromatography. The high-efficiency loading, sustained-release and permeability as transdermal delivery of GO-DEX-β-CD/DOC and Fe_3O_4/GO-Na/DOC were studied, and the encapsulation efficiency and drug loading of them were determined by centrifugation. The GO-DEX-β-CD/DOC and Fe_3O_4/GO-Na/DOC were applied onto the female mice skin in vitro and in vivo to develop the permeability of them. Results The encapsulation efficiency and drug loading of Fe_3O_4/GO-Na/DOC were higher than GO-DEX-β-CD/DOC, and its slow release property and permeability as transdermal delivery were better. The results showed that the accumulation permeation amount was(22.512 ± 0.715) μg after Fe_3O_4/GO-Na/DOC being applied over 90 h, DOC concentration in skin reached a peak at 15 min by the application of Fe_3O_4/GO-Na/DOC. After 5 h of administration, DOC concentration in the blood of female mice reached(76.886 ± 1.232) μg/m L. Conclusion The preparation techniques of Fe_3O_4/GO-Na/DOC was feasible with better sustained release and transdermal effect, which had a promising application prospect.
Objective To synthetize the new-type GO-DEX-β-CD/DOC and Fe_3O_4/GO-Na/DOC inclusion compound, and study its high-efficiency loading, sustained-release and permeability as transdermal delivery for docetaxel(DOC) composites. Methods The concentration of DOC was determined by high efficiency liquid chromatography. The high-efficiency loading, sustained-release and permeability as transdermal delivery of GO-DEX-β-CD/DOC and Fe_3O_4/GO-Na/DOC were studied, and the encapsulation efficiency and drug loading of them were determined by centrifugation. The GO-DEX-β-CD/DOC and Fe_3O_4/GO-Na/DOC were applied onto the female mice skin in vitro and in vivo to develop the permeability of them. Results The encapsulation efficiency and drug loading of Fe_3O_4/GO-Na/DOC were higher than GO-DEX-β-CD/DOC, and its slow release property and permeability as transdermal delivery were better. The results showed that the accumulation permeation amount was(22.512 ± 0.715) μg after Fe_3O_4/GO-Na/DOC being applied over 90 h, DOC concentration in skin reached a peak at 15 min by the application of Fe_3O_4/GO-Na/DOC. After 5 h of administration, DOC concentration in the blood of female mice reached(76.886 ± 1.232) μg/m L. Conclusion The preparation techniques of Fe_3O_4/GO-Na/DOC was feasible with better sustained release and transdermal effect, which had a promising application prospect.
引文
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[3]Xu C,Wu X,Zhu J,et al.Synthesis of amphiphilic graphite oxide[J].Carbon,2008,46(2):386-389.
[4]Tian B,Wang C,Zhang S,et al.Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide[J].ACS Nano,2011,5(9):7000-7009.
[5]Yang K,Wan J,Zhang S,et al.The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power[J].Biomaterials,2011,33(7):2206-2214.
[6]Zhang S,Yang K,Liu Z.Carbon nanotubes for in vivo cancer nanotechnology[J].Science China,2010,53(11):2217-2225.
[7]Raso E M G,Cortes M E,Sinisterra R D,et al.A new controlled release system of chlorhexidine and chlorhexidine:βcd inclusion compounds based on porous silica[J].J Incl Phenom Macrocycl Chem,2010,67(1/2):159-168.
[8]俞文英,马建琦,方杰,等.冬凌草甲素聚乙二醇功能化氧化石墨烯纳米粒的制备及抗结肠癌实验研究[J].中草药,2017,48(19):3954-3960.
[9]Liu Z,Robinson J T,Sun X M,et al.PEGylated nano-graphene oxide for delivery of water-insoluble cancer drugs[J].J Am Chem Soc,2008,130(33):10876-10882.
[10]Zhang K,Ang B T,Zhang L L,et al.Pyrolyzed graphene oxide/resorcinol-formaldehyde resin composites as highperformance supercapacitor electrodes[J].J Mater Chem,2011,21(8):2663-2670.
[11]Wilson R,Spiller D G,Beckett A,et al.Highly stable dextran-coated quantum dots for biomolecular detection and cellular imaging[J].Chem Mater,2010,22(23):6361-6369.
[12]申玉坤,申玉璞,张龙娇,等.功能性氧化石墨烯-β-环糊精/利多卡因包合物的制备及其质量评价[J].药物分析杂志,2014,34(10):1812-1816.
[13]申玉坤,龚连生,申玉璞,等.萘磺酸钠修饰的石墨烯基Fe3O4复合材料的制备与载药性能评价[J].中国医院药学杂志,2015,35(13):1168-1172.
[14]徐兴英,程江峰,单妍,等.氧化石墨烯的制备及其对盐酸多柔比星的高效装载和缓释性能[J].青岛科技大学学报,2011,32(5):472-477.
[15]Zhang L M,Xia J G,Zhao Q H,et al.Functional graphene oxide as s nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs[J].Small,2010,6(4):537-544.
[16]石可瑜,李朝兴,何炳林.磁导向阿霉素-羧甲基葡聚糖磁性毫微粒的研究[J].生物医学工程学杂志,2000,17(1):21-24.
[17]Sun X M,Liu Z,Dai H J,et al.Nano-graphene oxide for cellular imaging and drug delivery[J].Nano Res,2008,1(3):203-212.
[18]Ogiue-Ikeda M,Sato Y,Ueno S.A new method to destruct targeted cells using magnetizible beads and Pulsed magnetic force[J].IEEE T Nanobiosci,2003,2(4):262-265.
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