[关键词]
[摘要]
目的 制备苦参碱固体脂质纳米粒(matrine solid lipid nanoparticles,MA-SLN),并考察其药剂学性质与体外透皮给药行为。方法 采用微乳-低温固化法制备MA-SLN,以粒径、ζ电位和包封率为评价指标,通过正交试验筛选最佳处方和工艺;扫描电子显微镜(SEM)和透射电子显微镜(TEM)观察MA-SLN的形态;差示扫描量热法(DSC)和X射线衍射扫描(XRD)分析苦参碱在MA-SLN中的包埋状态;体外透皮实验考察药物的透皮及释放行为。结果 最佳处方工艺制得的MA-SLN包封率可达(56.12±0.82)%,激光粒度仪(DLS)检测MA-SLN的平均粒径为(196.31±6.26)nm,电位为(-37.18±2.36)mV。SEM和TEM显示MA-SLN呈规整的均匀球状或类球状结构;DSC和XRD检测可确定苦参碱可完全包裹在SLN内,苦参碱与SLN骨架材料相容性良好;体外透皮实验显示,9 h时累积透过量(ΔM)达到500 μg/cm2,且可持续释放至24 h,表明MA-SLN能够显著提高苦参碱的透皮吸收效率并具有较好的缓释行为。结论 采用微乳-低温固化法制备MA-SLN,其工艺简单、周期短、可控性高,易于产业化推广;且制成的MA-SLN性能优良、透皮吸收率高与缓释行为显著,可为透皮给药制剂提供一种较好的给药模型,为苦参碱进一步开发应用奠定基础。
[Key word]
[Abstract]
Objective To prepare matrine solid lipid nanoparticles (MA-SLN), investigated the pharmaceutical properties and in vitro transdermal behavior. Methods MA-SLN was prepared by microemulsion-low temperature curing method; The optimum formulation and process were selected by orthogonal test using particle size, ζ potential and encapsulation efficiency as evaluation indexes; The morphology of MA-SLN was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM); The embedding state of matrine in nanoparticles was analyzed by differential scanning calorimetry (DSC) and X-ray diffraction scanning (XRD); In vitro transdermal experiments were conducted to investigate the transdermal and release behavior of the drug. Results The encapsulation efficiency of MA-SLN prepared by the best prescription process was (56.12±0.82)%, laser particle size analyzer (DLS) showed that the average particle size of MA-SLN was (196.31±6.26) nm and the potential was (-37.18±2.36) mV; SEM and TEM showed that appearance of MA-SLN was spherical or nearly spherical; DSC and XRD showed that matrine could be completely encapsulated in nanoparticles and had good compatibility with SLN framework materials; Transdermal experiments showed that ΔM reached 500 μg/cm2 after 9 h, and sustainable released to 24 h, which indicated that MA-SLN can significantly improve the transdermal absorption efficiency of matrine and had good slow release behavior. Conclusion MA-SLN can be successfully prepared by microemulsion and low temperature curing method, it has the advantages of simple process, short preparation period, high controllability and easy to be industrialized and popularized. Moreover, MA-SLN has excellent performance, high transdermal absorption efficiency and significant sustained release behavior, which can provide a better model for transdermal drug delivery and lay a foundation for further development and application of matrine.
[中图分类号]
R283.6
[基金项目]
国家自然科学基金资助项目(82004075);陕西高校青年创新团队建设项目(陕教[2019]90号);陕西省中医药管理局科研课题(2019-ZZ-ZY010);陕西省科技厅面上项目(2020JM-610)