基于科塔杜提德可逆自组装的长效注射储存器,用于持续输送GLP-1葡萄糖受体激活剂,并控制突发释放
Bin Yang1, Durga Devalla1, Silvia Sonzini1
1Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Biomedical Campus, Cambridge, UK.
这项研究开发了一种新型的长效注射配方,用于双GLP-1 / 葡萄糖受体激动剂cotadutide. 在聚合物仓库中封装codatutide纤维显著延长了其半衰期,使每月剂量用于代谢疾病.
科学领域:
- 药理学 药理学是指药理学的学科.
- 生物材料科学 生物材料科学
- 药物输送系统 药物输送系统
背景情况:
- 科塔杜提德 (Cota) 是一种双重GLP-1和葡萄糖受体激动剂,用于代谢疾病,需要每天进行皮下注射.
- 患者对每日注射的不良遵守需要改善慢性疾病的药物输送策略.
研究的目的:
- 开发一种创新的持续释放式配方使用在现场形成仓库.
- 为了评估离子对达胺纤维特性和释放概况的影响.
- 评估新型配方的药理动力学特征和潜在的剂量频率.
主要方法:
- 在一个低分子量聚乳糖糖酸 (LWPLGA) 在现场成型仓库内封装可逆丁自组装纤维.
- 对纤维二次结构,形态和单体释放的阴离子 (Na+,Ca2+,Zn2+) 影响的研究.
- 在老鼠中进行的药理动力学研究比较了新型仓库配方与即时释放的杜丁.
主要成果:
- 具有层次结构的纤维 (扭曲的纤维,带) 和β-sheet的二次结构证明了受控的爆裂释放.
- 在老鼠中,Ca2+纤维/LWPLGA储存配方显示Cmax比立即释放的codatutide降低了60倍.
- 血半衰期延长到100小时,使得在老鼠中具有稳定的治疗度的潜在14天剂量间隔.
结论:
- 开发的LWPLGA仓库配方提供了一个有前途的持续交付策略,用于cotadutide.
- 这种长效注射剂 (LAI) 方法可以将短半衰期转化为不太频繁的剂量方案的候选者.
- 该配方有潜力改善患者的服从性和慢性代谢性疾病管理的舒适性.
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