苦参碱固体脂质纳米粒的制备及其体外透皮研究

Preparation and in vitro transdermal study on solid lipid nanoparticles of matrine

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500μg/cm^(2),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。

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,ζpotential 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 thatΔM reached 500μg/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.