洛美沙星透皮吸收制剂对小鼠皮肤表皮结构的影响

Effect of percutaneous absorption preparation of Lomefloxacin with laurocapram on epidermal morphology of mouse skin

以含氮酮的洛美沙星透皮吸收制剂为模型药物,昆明种(KM)雄性小鼠在体皮肤为研究材料,设计6个试验时间段(涂药后2.25、4.5、9、18、36和72 h),综合运用光镜(LE)、扫描电镜(SEM)和透射电镜(TEM)技术,观测经透皮吸收制剂作用后小鼠皮肤表皮及毛囊结构的变化,探讨氮酮促进洛美沙星透皮吸收的机理.结果表明,氮酮通过以下途径促进药物透皮吸收:作用于表皮角质层细胞间脂质,使角质层细胞间距增大,从而引起角质层外层细胞易于脱落,皮肤角质层变薄,减弱表皮对药物的屏障作用;作用于细胞内基质,引起基底角质层肿胀,增加了角质细胞的水化程度和药物的存储空间;作用于毛囊,使毛囊口附近角质疏松、脱落,使药物易于经毛囊途径吸收,但毛囊在本研究中为非主要渗透途径.研究还表明,单次应用该制剂对小鼠皮肤结构的影响超过72 h;由该制剂引起小鼠皮肤结构的改变是个非损伤性可复过程.

To clarify the mechanism of action of laurocapram in Lomefloxacin pereutaneous absorption preparation, the effect of this preparation with laurocapram on the epidermal morphology was investigated in vivo using Kunming male mouse＇s skin as a model membrane. The abdominal skin of the mice were excised at 2.25 h, 4.5 h, 9 h, 18 h, 36 h and 72 h after the treatments respectively. All the collected skins were examined comparatively by light microscopy （LM） , scanning electron microscopy （SEM） and transmission electron microscopy （TEM）. The results suggested the mechanism of laurocapram as a penetration enhancer is as follows; （1） Laurocapram disrupts the highly ordered lipid structure of stratum corneum （ SC ） and makes it loose, which decreases the barrier function of skin for the trandermal absorption of this preparation. （2） Laurocapram penetrating into the intracellular matrix of SC cells breaks down and fluidizes the filaggrin matrix protein, and swells the dermal SC, which increase the free volume of drug and water content in the SC. （ 3 ） Meanwhile, laurocapram makes the SC around hair follicles loose and easy to exfoliate, which results in transdermal absorption of this preparation by hair follicle path. But hair follicle is a minor penetration route for this preparation. This study also discovered that the barrier structure of SC is still in the state of recovery at 72 hours after medication and the change of epidermis caused by this preparation is a non-damnifing and reversible course.