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

Studies on high-efficiency loading, sustained-release and permeability as transdermal delivery of graphene oxide to docetaxel composites

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(Fe3O4/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Fe3O4/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Fe3O4/GO-Na/DOC经雌鼠皮肤给药的渗透性。结果 Fe3O4/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Fe3O4/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5 h后,雌鼠血液中检测出DOC质量浓度达到(76.886±1.232)μg/mL。结论 Fe3O4/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 Fe3O4/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 Fe3O4/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 Fe3O4/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 Fe3O4/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 Fe3O4/GO-Na/DOC being applied over 90 h, DOC concentration in skin reached a peak at 15 min by the application of Fe3O4/GO-Na/DOC. After 5 h of administration, DOC concentration in the blood of female mice reached (76.886 ±1.232)μg/mL. Conclusion The preparation techniques of Fe3O4/GO-Na/DOC was feasible with better sustained release and transdermal effect, which had a promising application prospect.