生物活性多肽TVA促进蛋白类大分子经皮渗透行为的研究  

Promotion on percutaneous permeation behavior of protein macromolecules by bioactive polypeptide TVA

作　　者：杨晓斌 贝煜 陈颖之 黄亚东 项琪 张蜀[1] YANG Xiaobin;BEI Yu;CHEN Yingzhi;HUANG Yadong;XIANG Qi;ZHANG Shu(New Drug Research and Development Center,Guangdong Pharmaceutical University,Guangzhou 510006,China;Biopharmaceutical R&D Center of Jinan University Co.,Ltd.,Guangzhou 510632,China;Guangzhou Kingtest Technology Co.,Ltd.,Guangzhou 510330,China)

机构地区：[1]广东药科大学新药研发中心,广东广州510006 [2]广州暨南大学医药生物技术研究开发中心有限公司,广东广州510632 [3]广州金至检测技术有限公司,广东广州510330

出　　处：《沈阳药科大学学报》2022年第4期447-453,共7页Journal of Shenyang Pharmaceutical University

基　　金：2018年省级促进经济发展专项资金(海洋经济发展用途)项目(34118003);广州市科技计划项目(201803010044);天河区科技计划项目(201704YG066)。

摘　　要：目的评价生物活性多肽TVA(Tvigour A)及其促进大分子蛋白皮肤渗透的行为。方法分别在细胞、在体大鼠皮肤和健康志愿者手臂皮肤进行TVA自身及促进大分子蛋白透皮吸收的能力测试实验。激光共聚焦观察TVA携带血小板源性生长因子(platelet derived growth factor,PDGF)进入大鼠嗜铬神经瘤细胞(pheochromocytoma cells,PC12)的经时过程;荧光显微镜观察TVA在SD大鼠皮肤内的分布;胶带粘贴法结合ELISA测定TVA携带的表皮细胞生长因子(epidermal growth factor,EGF)渗透到健康志愿者手臂皮肤表皮的含量。结果生物活性多肽TVA能携带大分子多肽/蛋白PDGF进入PC12细胞;在大鼠皮肤表皮层和真皮层均观察到绿色荧光蛋白(enhanced green fluorescent protein,EGFP)标记的TVA;D-squame R盘所取各层皮肤角质细胞中的基因重组人表皮生长因子(recombinant human epidermal growth factor,rhEGF),rhEGF含量在各时间点均比单rhEGF水溶液组高。结论生物活性多肽TVA可以提高大分子药物进入细胞的数量,提高大分子药物的透皮吸收,可作为大分子化合物的皮肤促渗剂。Objective To evaluate the biologically active peptide TVA(Tvigour A)and its promotion on percutaneous penetration of macromolecular proteins.Methods The transdermal absorption ability of TVA and its promoting effect to macromolecular proteins respectively on cells,the in vivo rat skin and arm skin of healthy volunteers were tested.The time course of TVA carrying platelet derived growth factor(PDGF)into rat pheochromocytoma cells(PC12)was observed by laser confocal microscope.The distribution of TVA in SD rat skin was observed by fluorescence microscope.The amount of epidermal growth factor(EGF)carried by TVA penetrated into the skin epidermis of healthy volunteers was determined by adhesive tape method combined with ELISA.Results The biologically active peptide TVA could carry more PDGF into PC12,and the enhanced green fluorescent protein EGFP-labeled TVA was observed in the epidermis and dermis of rat skin.The recombinant human epidermal growth factor(rhEGF)content in the keratinocytes of each skin layer taken from the D-squame R disc was higher than the rhEGF aqueous solution group at each time point.Conclusion The biologically active polypeptide TVA can increase the amounts of macromolecular drugs into cells and improve the transdermal absorption of macromolecular drugs.TVA can be used as a skin penetration enhancer for macromolecular compounds.

关 键 词：生物活性多肽Tvigour A 细胞膜渗透 生物大分子 皮肤促渗剂 

分 类 号：R96[医药卫生—药理学]