阴道用苦参柔性脂质体泡沫气雾剂的制备研究

Preparation of foam aerosol of Sophorae flavescentis Radix loaded flexible liposome

目的制备包封苦参脂溶性和水溶性活性部位的柔性脂质体,再将苦参柔性脂质体制备成泡沫气雾剂;研究其体外透黏膜给药的特点,并与洗剂和普通气雾剂进行比较。方法将苦参分步提取得到其脂溶性和水溶性活性部位;采用薄膜分散法,将脂溶性和水溶性活性部位分别溶于磷脂相和内水相制备柔性脂质体;采用原子力显微镜、透射电镜和光子相关光谱仪考察其药剂学性质,并用高效液相色谱法和挤压法考察苦参柔性脂质体的包封率和变形性。将苦参柔性脂质体制备成泡沫气雾剂,并考察其泡沫的膨胀情况;采用离体猪阴道组织为模型,考察苦参柔性脂质体泡沫气雾剂的体外透黏膜给药,并与苦参的洗剂和普通气雾剂进行比较。结果苦参柔性脂质体为圆球或椭球形,内部具有层状囊泡结构;粒径为(150±19)nm,表面电位为(-40±2.8)mV;对苦参碱的包封率为(78.21±0.65)%,在0.8 MPa下的变形性为(92.43±5.71)%。泡沫气雾剂的泡沫具有缓慢膨胀过程,其在体外条件下能持续约70 min。8.0 h时,苦参柔性脂质体泡沫气雾剂中苦参碱透过阴道黏膜的累积透过量分别为苦参洗剂和普通气雾剂的3.18与1.79倍。结论 柔性脂质体泡沫气雾剂能够促进药物透过阴道黏膜并利于药物在阴道组织中形成药物储库。

AIM To prepare the foam aerosol of Sophorae flavescentis Radix（SFR） through the encapsulated liposoluble and hydrosoluble active parts to form SFR loaded flexible used for vaginitis,and compared with lotion and common aerosols.METHODS The liposoluble and hydrosoluble active parts of SFR were extracted.Liposomes were prepared by thin-film homogenization method,briefly,the liposoluble and hydrosoluble active parts were dissolved in phospholipid phase and water phase.Their physical properties（entrapment rate and deformability） were evaluated by the atomic force microscope,transmission electron microscope and photon correlation spectrometer.The swelling degree and duration of foam aerosol were also valuated.Pig vaginas were used to analyze the characteristics of matrine released from foam aerosol in vitro,and compared with lotion and common aerosols.RESULTS SFR loaded flexible liposomes had a closed spherical or elliptical shape with multi-lamellar vesicles.The calculated mean size was（150±19） nm,the zeta potential values of（-40±2.8） mV.The matrine entrapment capacity（calculated as percentages of total drug） was（78.21±0.65）%.Under the pressure of 0.8 MPa,the deformability of SFR loaded flexible liposomes was（92.43±5.71）%.A slowly expansion process of the foam was observed,and the foam could sustain 70 min.At 8.0 h,the accumulated permeation amount of matrine from the foam aerosol was 3.18 and 1.79 folds than that of lotion and common aerosols,respectively.CONCLUSION The foam aerosol of SFR loaded flexible liposomes could greatly increase the vaginal mucosa permeability and the amount of matrine.