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.
引文
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