介孔二氧化硅纳米材料的皮肤安全性研究

Study on the Safety of Mesoporous Silica Nanomaterials to Skin

目的:评价介孔二氧化硅纳米材料(MSNs)的皮肤渗透性、刺激性及过敏性。方法:在体透皮实验中,将分别载不同量(0.75%和3%,W/W)MSNs和氨基修饰的MSNs(NH2-MSNs)的凝胶涂布于大鼠背部皮肤,考察24 h后皮肤中硅含量及在皮肤组织中的分布(n=4);皮肤刺激性实验中,将分别载3%MSNs和NH2-MSNs的凝胶多次(1次/d,共7 d)涂布于家兔完整皮肤及破损皮肤,采用同体左右侧自身对照,给药期间每日观察局部皮肤红斑及水肿情况(n=4);皮肤过敏性实验中,于实验第1、7、14天将载3%MSNs和NH2-MSNs的凝胶、凝胶基质和1%2,4-二硝基氯代苯溶液(阳性对照)分别涂布于豚鼠背部皮肤左侧致敏,于末次致敏后14 d(第28天)同法涂药于右侧激发接触,以是否出现红斑或水肿为指标,观察局部皮肤的过敏反应(n=6)。结果:载0.75%、3%MSNs的凝胶致皮肤中硅含量分别为(10.812±3.963)、(22.050±5.721)μg/g,载0.75%、3%NH2-MSNs的凝胶致皮肤中硅含量分别为(7.799±2.068)、(16.416±3.221)μg/g,透射电镜显示MSNs能跨过皮肤屏障,进入真皮层;完整皮肤和破损皮肤均未出现红斑或水肿现象;与阳性对照比较,载MSNs及NH2-MSNs的凝胶均未导致豚鼠皮肤出现红斑或水肿。结论:MSNs作为局部施药载体具有良好的皮肤安全性。

OBJECTIVE：To evaluate the skin permeation in vivo,irritation and hypersensitivity of mesoporous silica materials（MSNs）. METHODS：In vivo transdermal experiments：0.75% and 3% MSNs-loaded gel and NH2-MSNs-loaded gel were coated on skin of rats＇ back respectively;the content of silicon and its distribution in skin were investigated within 24 h（n=4）. The skin irritation test：the intact and damaged skin of rabbits was coated by 3% MSNs-loaded and 3% NH2-MSNs-loaded gel repeatedly（once a day,for 7days）;by comparison rabbits＇ skin left side with right side,the edema and erythema of topical skin were observed every day during medication（n=4）. The skin allergy test：the left side skin of guinea pigs＇ back was coated by 3%MSNs-loaded and 3% NH2-MSNs-loaded gel,gel matrix and 2,4-dinitrochlorobenzene（positive control）on the 1st,7th and 14 th day;14 days after last sensitization（28th day）,the right side skin of guinea pigs＇ back was coated with same drug by same method;the allergic reaction was observed according to edema and erythema（n=6）. RESULTS：The contents of silicon in skin treated with 0.75% or 3% MSNs-loaded gel were（10.812±3.963）μg/g and（22.050±5.721）μg/g;those of skin treated with 0.75% or3% NH2-MSNs-loaded gel were（7.799±2.068）μg/g and（16.416±3.221）μg/g. TEM showed that MSNs could enter the dermis through passing skin barrier. No edema and erythema was found in intact and damaged skin. Compared with positive control,MSNs-loaded and NH2-MSNs-loaded gel didn＇t result in erythema or edema of guinea pigs＇ skin. CONCLUSIONS：MSNs shows good safety to skin as vehicle for topical drug delivery.