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Updated: Jul 7, 2025

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可注射生物降解的储存器用于控制的反意义寡核酸的皮下输送,每月给药量超出每月给药量
Asmaa McGowan1, Peter Gennemark2,3, Marceline Akieh-Pirkanniemi1
1DelSiTech Ltd., PharmaCity, Itäinen Pitkäkatu 4 B, 20520 Turku, Finland.
新的可生物降解的二氧化矩阵能够持续释放反感性寡核酸 (ASOs) 超过四周. 这一创新可以减少剂量的频率,改善ASO治疗的患者方便性和治疗结果.
科学领域:
- 生物材料科学 生物材料科学
- 药物输送系统 药物输送系统
- 氧核酸治疗药物 治疗药物
背景情况:
- 反感性寡核酸 (ASOs) 通常是每周或每月一次的皮下注射.
- 较少频繁的ASO剂量可以提高患者的坚持和治疗疗效.
- 高水溶性和ASO剂量要求限制了持续释放配方选择.
研究的目的:
- 开发和评估一种新的生物降解基矩阵,用于持续的皮下ASO输送.
- 评估ASO加载的基板的释放动力学和体内性能.
- 为了研究延长剂量间隔超出每月一次的可能性.
主要方法:
- 在可生物降解,无孔的基层中制备ASOs.
- 在生体内对大鼠进行药理动力学研究,以评估药物释放特征.
- 测量肝脏ASO度,mRNA淘汰和循环蛋白减少.
主要成果:
- 基质证明了零级释放in vivo至少4周,ASO负载高达100毫克/毫升,没有初始爆发.
- 较高的药物负载导致在第一周内大量的突发释放.
- 肝脏ASO度与玻尿酸剂量相当;迷你输注显示肝脏暴露较高,有效减少mRNA/蛋白质.
结论:
- 可生物降解的二氧化矩阵可以在长时间内在体内实现ASO的持续零序释放.
- 这项技术支持每月少于一次的ASO管理的可行性.
- 通过皮下注射慢释放ASO的管理表明生产性肝脏吸收和治疗效果.
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