CAJ | 학술논문

目的研究125Ⅰ标记的树枝状高分子纳米材料聚酰胺-胺(PAMAM)在小鼠体内的生物分布.方法通过羟基琥珀酰亚胺将酪氨酸连接到4代PAMAM上,再对PAMAM进行125Ⅰ标记,透析法对标记化合物进行纯化,放射性薄层扫描对标记物进行标记率、放化纯度及稳定性检测.将125Ⅰ-PAMAM经尾静脉注射人小鼠体内,分别在1、4、8、24、48 h时对小鼠进行活体成像,并取主要脏器进行放射性计数.结果磁共振氢谱法检测结果显示,每个PAMAM分子上约连接了两个酪氨酸分子,标记率约为56％,放化纯度＞98％,标记化合物具有良好的稳定性,体外放置72 h放化纯度仍＞90％.小动物活体成像结果显示,PAMAM主要聚集在肝脏部位.各组织的放射性计数与显像结果基本一致,主要分布在肝、肾和脾中,而且体内代谢较慢,48 h时在小鼠体内仍有较高分布.结论未经修饰的PAMAM在肝、肾及脾中大量聚集,体内代谢缓慢,不适合直接作为药物载体进行使用,需进行化学修饰来加速体内代谢,防止体内蓄积从而引起不良反应.
목적 연구125Ⅰ표기적수지상고분자납미재료취선알-알(PAMAM)재소서체내적생물분포.방법 통과간기호박선아알장락안산련접도4대PAMAM상,재대PAMAM진행125Ⅰ표기,투석법대표기화합물진행순화,방사성박층소묘대표기물진행표기솔、방화순도급은정성검측.장125Ⅰ-PAMAM경미정맥주사인소서체내,분별재1、4、8、24、48 h시대소서진행활체성상,병취주요장기진행방사성계수.결과 자공진경보법검측결과현시,매개PAMAM분자상약련접료량개락안산분자,표기솔약위56％,방화순도＞98％,표기화합물구유량호적은정성,체외방치72 h방화순도잉＞90％.소동물활체성상결과현시,PAMAM주요취집재간장부위.각조직적방사성계수여현상결과기본일치,주요분포재간、신화비중,이차체내대사교만,48 h시재소서체내잉유교고분포.결론 미경수식적PAMAM재간、신급비중대량취집,체내대사완만,불괄합직접작위약물재체진행사용,수진행화학수식래가속체내대사,방지체내축적종이인기불량반응.
Objective To investigate the biodistribution of 125Ⅰ labeled dendrimer nanomaterialpolyamidoamine (PAMAM) in mice.Methods Tyrosine was conjugated to four generation PAMAM by NHydroxysuccinimide,then 125Ⅰ was labeled on PAMAM with chloramines-T method,and purified by dialysis.Labeling rate,radiochemical purity and stability of 125Ⅰ-PAMAM were detected by radioactive thin layer chromatography scanning.The gamma imaging and biodistribution were detected by in vivo imaging system and gamma counter at one,four,eight,twenty-four and forty-eight hours after intravenous injection.Results The IH nuclear magnetic resonance results showed that about two tyrosines were conjugated to PAMAM.The 125Ⅰ labeling rate was about 56％ and radiochemical purity was more than 98％.The radiochemical purity of labeled compound remained more than 90％ at 72 hours in vitro.In vivo imaging results showed that PAMAM was mainly accumulated in liver periphery.The gamma counter results showed that PAMAM mainly accumulated in liver,kidney and spleen,the excretion of PAMAM was slow and there has high dose of PAMAM in mice at 48 hours.Conclusion PAMAM with no chemical modification was mainly accumulated in liver,kidney and spleen,and the excretion of PAMAM was slow,so PAMAM is not fit as drug carrier.PAMAM need to chemical modification to accelerate excretion and prevent the emergence of toxicity caused by accumulation in body.