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

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.

Keywords: DNase; drug delivery; liposomes; microfluidics; nanoparticles; neutrophil extracellular traps.