抗人白介素-8鼠单抗乳膏经皮吸收治疗银屑病的研究  

Study on transdermal absorption of mouse monoclonal antibody against human interleukin-8 cream for the treatment of psoriasis

作　　者：张袁园 孟雪 王鑫颖 王红霞 王伟[1] 高兴华[3] 汪晴[1] ZHANG Yuanyuan;MENG Xue;WANG Xinying;WANG Hongxia;WANG Wei;GAO Xinghua;WANG Qing(Department of Pharmacy,School of Chemical Engineering,State Key Laboratory of Fine Chemicals,Dalian University of Technology,Liaoning Dalian 116024,China;Research and Development Department,Dalian Kexiang Technology Development Company,Liaoning Dalian 116085,China;Department of Dermatology,The First Hospital of China Medical University,Liaoning Shenyang 110002,China)

机构地区：[1]大连理工大学化工学院药学系,精细化工国家重点实验室,辽宁大连116024 [2]大连科翔科技开发有限公司研发部,辽宁大连116085 [3]中国医科大学附属第一医院皮肤科,辽宁沈阳110002

出　　处：《中国医院药学杂志》2023年第20期2264-2269,共6页Chinese Journal of Hospital Pharmacy

摘　　要：目的:研究抗人白细胞介素-8鼠单抗(MMA-8)乳膏的皮肤渗透性及其对银屑病样模型小鼠的治疗效果。方法:采用体外扩散池法和皮肤组织切片检测MMA-8乳膏的皮肤渗透性,并通过荧光显微成像技术进行验证。使用外涂咪喹莫特建立银屑病样小鼠模型,并评价了MMA-8乳膏治疗银屑病的药理活性。结果:体外经皮渗透实验表明,小鼠皮肤组织中MMA-8的24 h累积渗透量(Q24 h)达(110.88±24.93)ng·cm^(-2),显著高于大鼠组[(10.07±6.35)ng·cm^(-2)]和裸鼠组[(9.18±4.70)ng·cm^(-2)](P<0.01)。人体正常皮肤涂抹给药组的Q24 h分别为(11.69±3.18)ng·cm^(-2)(全皮)和(91.30±34.65)ng·cm^(-2)(去角质层皮肤),搓揉给药组分别为(46.92±23.44)ng·cm^(-2)(全皮)和(82.46±5.39)ng·cm^(-2)(去角质层皮肤)。皮肤组织切片显示MMA-8在皮肤中含量最高的位置为0~90μm(小鼠皮肤)和0~600μm(人体皮肤)。荧光显微成像结果显示药物在全皮中主要滞留在角质层,而在去角质层皮肤中到达真皮。药效学实验表明,与模型组相比,MMA-8组小鼠银屑病皮损严重程度指数评分、银屑病病理评分以及皮肤中的MIP-2含量均显著降低(P<0.01)。结论:MMA-8乳膏在全皮中主要通过毛囊经皮渗透,角质层对渗透有明显的阻碍作用。MMA-8在皮肤中滞留部位主要为表皮层和真皮层上层。MMA-8乳膏可降低银屑病样皮损处的MIP-2含量,改善小鼠皮损状态,从而起到治疗银屑病的作用。OBJECTIVE To investigate the skin permeability of mouse monoclonal antibody against human interleukin-8(MMA-8)cream and therapeutic effect on imiquimod-induced psoriatic mouse model.METHODS The skin permeability of MMA-8 cream was studied by in vitro diffusion cell method and skin tissue sections,and verified by fluorescence microscopy imaging.The efficacy of MMA-8 cream was evaluated by the imiquimod-induced psoriatic mouse model.RESULTS The in vitro percutaneous penetration test showed that the 24-h cumulative penetration(Q24 h)of MMA-8 in mouse skin reached(110.88±24.93)ng·cm^(-2),which was significantly higher than that of the rat group[(10.07±6.35)ng·cm^(-2)]and nude mice group[(9.18±4.70)ng·cm^(-2)](P<0.01).The Q24 h of the human skin group applying cream by smearing was(11.69±3.18)ng·cm^(-2)(intact skin)and(91.30±34.65)ng·cm^(-2)(stripped skin).As for the human skin group applying cream by rubbing was(46.92±23.44)ng·cm^(-2)(intact skin)and(82.46±5.39)ng·cm^(-2)(stripped skin).The areas with the highest levels of MMA-8 in the skin were found to be 0~90μm(mouse skin)and 0~600μm(human skin)by skin tissue sections.The results of fluorescence microscopy showed that the drug was mainly retained in the stratum corneum in the intact skin,but could reach the dermis in the stripped skin.According to the pharmacodynamics experiment,compared with the model group,the psoriasis area severity index score,psoriasis pathology score and MIP-2 content in the skin in MMA-8 group were significantly decreased(P<0.01).CONCLUSION The penetration path of MMA-8 cream in the intact skin is mainly through the hair follicle,and the stratum corneum has an obvious hindering effect on the penetration.The highest retention areas of MMA-8 in the skin are the epidermis and the upper dermis.MMA-8 cream can reduce the content of MIP-2 in psoriasis-like skin lesions,improve the lesion status in mice,thus plays a role in the treatment of psoriasis.

关 键 词：抗人白细胞介素-8鼠单抗乳膏 银屑病 体外渗透 皮肤滞留 银屑病样小鼠模型 

分 类 号：R9455[医药卫生—微生物与生化药学]