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延长循环半衰期的脂质体 DNA 酶 I 制剂的优化。

Optimization of a Liposomal DNase I Formulation with an Extended Circulating Half-Life.

机构信息

Faculté de Pharmacie, Université de Montréal, 2940 Chemin de Polytechnique, Montréal, Québec Canada H3T 1J4.

出版信息

Mol Pharm. 2022 Jun 6;19(6):1906-1916. doi: 10.1021/acs.molpharmaceut.2c00086. Epub 2022 May 11.

Abstract

Drug delivery systems such as liposomes are widely used to stabilize and increase the plasma half-life of therapeutics. In this article, we have investigated two strategies to increase the half-life of deoxyribonuclease I, an FDA-approved enzyme used for the treatment of cystic fibrosis, and a potential candidate for the reduction of uncontrolled inflammation induced by neutrophil extracellular traps. We demonstrate that our optimized preparation procedure resulted in nanoparticles with improved plasma half-life and total exposure relative to native protein, while maintaining enzymatic activity.

摘要

药物传递系统(如脂质体)被广泛用于稳定和延长治疗剂的血浆半衰期。在本文中,我们研究了两种策略来增加脱氧核糖核酸酶 I 的半衰期,脱氧核糖核酸酶 I 是一种已获得 FDA 批准的酶,用于治疗囊性纤维化,也是减少中性粒细胞胞外陷阱引起的失控性炎症的潜在候选药物。我们证明,我们优化的制备程序可得到具有改善的血浆半衰期和总暴露的纳米颗粒,与天然蛋白相比,同时保持酶活性。

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