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首页> 外文会议>Society for Biomaterials annual meeting and exposition >Liver targeted Primaquine drugamers for the treatment of malaria in high risk settings
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Liver targeted Primaquine drugamers for the treatment of malaria in high risk settings

机译：肝靶向Primaquine药物治疗剂，用于高风险环境中的疟疾治疗

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Polymerizable prodrug PQ monomer carrying a hydrolytic linker and a liver targeting GalNAc monomer were successfully made and incorporated into three structurally different macromolecular drugamer constructs. Two materials - copolymer and RSN were selected and taken forward due to their drug release profiles fitting the project. In vivo PK profiles showed that the copolymer and RSN were quickly cleared from the blood and accumulated in the liver providing sustained delivery of PQ, a desirable property aimed to overcome the hemolytic toxicity. Toxicity studies conducted with two G6PD deficiency humanized mouse models -Mediterranean and African variants exhibited no hemolytic toxicity, often noted with free PQ administration. Absence of hemolytic toxicity combined with sustained release of PQ at the target liver site strongly demonstrate the GalNAc targeted PQ drugamer platform as a safe promising system with better therapeutic efficacy for treating malaria, particularly in high-risk G6PD deficient patients.
机译：成功地制备了带有水解接头的可聚合前药PQ单体和靶向肝脏的GalNAc单体，并将其掺入了三种结构不同的大分子药物结构中。选择了两种材料-共聚物和RSN，因为它们的药物释放曲线适合该项目。体内PK曲线表明，共聚物和RSN迅速从血液中清除，并积聚在肝脏中，提供了PQ的持续释放，这是旨在克服溶血毒性的理想特性。用两种G6PD缺乏症人源化小鼠模型进行的毒性研究-地中海和非洲变体没有溶血毒性，通常通过免费PQ给药即可发现。溶血毒性的缺乏与目标肝脏部位PQ的持续释放相结合，强烈证明了GalNAc靶向的PQ药物平台是一种安全的，有前途的系统，具有更好的治疗疟疾的疗效，特别是在高危G6PD缺乏症患者中。

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