负极性聚丙烯驻极体美洛昔康贴剂对大鼠皮肤结构的影响

Influences of negative polypropylene electret meloxicam patch on percutaneous absorption of drug in rat

目的：比较负极性聚丙烯驻极体和驻极体美洛昔康贴剂对SD大鼠皮肤结构变化的影响，探讨负极性驻极体美洛昔康贴剂的透皮促渗机制。方法：以美洛昔康为模型药物，利用药剂学方法和栅控恒压电晕充电技术制备负极性驻极体美洛昔康贴剂，通过光镜、扫描电镜观察驻极体及其驻极体美洛昔康贴剂对大鼠皮肤结构的影响。结果：负极性聚丙烯驻极体及其驻极体美洛昔康贴剂具有良好的电荷储存稳定性，在12h内两者的等效表面电位均保持其初始电位的近85％以上；负极性驻极体产生的静电场能使大鼠皮肤角质层脂质分子的定向排列发生改变，并使细胞间隙增宽，毛囊口径扩大；驻极体美洛昔康贴剂作用大鼠皮肤2～4h后，出现皮肤角质层变薄，角质层之间连接松散，角质层外层细胞容易脱落，皮肤表面出现不连续性及裂隙增加、皮肤角质层层状类脂层的排列结构发生改变和毛囊口拓宽等现象。结论：聚丙烯驻极体美洛昔康贴剂产生的恒定静电场能减弱皮肤屏障功能、增加皮肤的通透性和加快药物的渗透速度，聚丙烯驻极体美洛昔康贴剂在透皮给药方面具有广阔的应用前景。

Objective： To compare the influences of the morphological changes of the skin structure by negative polypropylene （PP） electret and PP electret meloxicam patch in rat, and to investigate the mechanism of negative electret meloxieam patch in enhancing transdermal drug delivery. Methods： Pharmacal method and grid-controlled constant corona charge technology were applied to make electret meloxicam patch. Using meloxieam as model drug, its morphological changes of the rat skin structure were investigated by means of light microscopy and scanning electron microscopy. Results： （1） Negative PP electret as well as its PP meloxicam patch electret exhibited a good charge storage stability, both of the surface potential kept 85% of the incipient potencial during the period of 1-12 hours; （2） The long-term electrostatic field that electret produced could change the arrangement of laminar lipid of stratum corneum, widen epidermal cells and broaden hair follicles; （3） The morphological study of rat skin after PIP meloxicam patch electret treatment for 2-4 h indicated attenuation of the stratum corneum, looseness of compact structure of stratum corneum, desquamation of stratum corneum from epidermis, increasing of epidermal cranny, alteration of fluid properties of the stratum corneum lipid and dilatation of hair follicles. Conclusion： The long-term electrostatic field that electret produced could greatly reduce the barrier function of stratum eorneum, increase the dermatic permeability and help to increase the permeation rate of drug through skin. Therefore, PP electret meloxieam patch will be of great potential drug transdermal formulation preparation in the near future.