Preparation of liposomal amiodarone and investigation of its cardiomyocyte-targeting ability in cardiac radiofrequency ablation rat model

作者：Ying Zhuge, Mu-Qing Xie, Lin Li, Fang Wang, Feng Gao, Zhifeng Zheng · 发表于：International Journal of Nanomedicine · 年份：2016 · DOI：10.2147/ijn.s98815 · 被引用次数：35 · 研究领域：RNA Interference and Gene Delivery、Nanoparticle-Based Drug Delivery、Dendrimers and Hyperbranched Polymers

The objective of this study was to develop an amiodarone hydrochloride (ADHC)-loaded liposome (ADHC-L) formulation and investigate its potential for cardiomyocyte targeting after cardiac radiofrequency ablation (CA) in vivo. The ADHC-L was prepared by thin-film method combined with ultrasonication and extrusion. The preparation process was optimized by Box-Behnken design with encapsulation efficiency as the main evaluation index. The optimum formulation was quantitatively obtained with a diameter of 99.9±0.4 nm, a zeta potential of 35.1±10.9 mV, and an encapsulation efficiency of 99.5%±13.3%. Transmission electron microscopy showed that the liposomes were spherical particles with integrated bilayers and well dispersed with high colloidal stability. Pharmacokinetic studies were investigated in rats after intravenous administration, which revealed that compared with free ADHC treatment, ADHC-L treatment showed a 5.1-fold increase in the area under the plasma drug concentration-time curve over a period of 24 hours (AUC0-24 h) and an 8.5-fold increase in mean residence time, suggesting that ADHC-L could facilitate drug release in a more stable and sustained manner while increasing the circulation time of ADHC, especially in the blood. Biodistribution studies of ADHC-L demonstrated that ADHC concentration in the heart was 4.1 times higher after ADHC-L treatment in CA rat model compared with ADHC-L sham-operated treatment at 20 minutes postinjection. Fluorescence imaging studies fu...