A novel long-acting azathioprine polyhydroxyalkanoate nanoparticle enhances treatment efficacy for systemic lupus erythematosus with reduced side effects

作者：Jin Hu, Min Wang, Xinyue Xiao, Bo Zhang, Qiu Xie, Xinjie Xu, Shengjie Li, Zhifa Zheng, Dai‐Xu Wei, Xuan Zhang · 发表于：Nanoscale · 年份：2020 · DOI：10.1039/d0nr01308k · 被引用次数：68 · 研究领域：Systemic Lupus Erythematosus Research、Monoclonal and Polyclonal Antibodies Research、Immune Cell Function and Interaction

Chemical immunosuppressants have been widely used for the treatment of systemic lupus erythematosus (SLE). However, these small chemical drugs suffer from poor solubility, short circulating half-life and adverse side effects. One of the most effective strategies to extend the circulating time is loading drugs into nanocarriers to form nanomedicines, which is of particular interest for the treatment of cancer and viral diseases but has seldom been applied to autoimmune disorders. Herein, we successfully developed an easy but general drug delivery platform based on the new biocompatible polyhydroxyalkanoate (PHA) terpolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBVHHx). In this proof of concept study, we loaded the PHBVHHx nanocarrier with the immunosuppressant azathioprine (AZA) for SLE therapy for the first time. The AZA-PHA nanoparticles possessed ∼30% cytotoxicity and slow clearance from the kidneys. In a murine SLE model, AZA-PHA nanoparticles exhibited superior therapeutic efficacy to AZA and AZA-polylactic acid (PLA) nanoparticles without appreciable toxicity. This delivery system may provide a new and general platform for the development of nanomedicines with enhanced therapeutic efficacy and reduced side effects in SLE therapy.