Abstract：
Since phospholipids have an important effect on the size, surface potential and hardness of liposomes that decide their in vivo fate after inhalation, this research has systematically evaluated the effect of phospholipids on pulmonary drug delivery by liposomes. In this study, liposomes composed of neutral saturated/unsaturated phospholipids, anionic and cationic phospholipids were constructed to investigate how surface potential and the degree of saturation of fatty acid chains determined their mucus and epithelium permeability both in vitro and in vivo. Our results clearly indicated that liposomes composed of saturated neutral and anionic phospholipids possessed high stability and permeability, compared to that of liposomes composed of unsaturated phospholipids and cationic phospholipids. Furthermore, both in vivo imaging of fluorescence-labeled liposomes and biodistribution of salvianolic acid B (SAB) that encapsulated in liposomes were performed to estimate the effect of phospholipids on the lung exposure and retention of inhaled liposomes. Finally, inhaled SAB-loaded liposomes exhibited enhanced therapeutic effects in a bleomycin-induced idiopathic pulmonary fibrosis mice model via inhibition of inflammation and regulation on coagulation-fibrinolytic system. Such findings will be beneficial to the development of inhalable lipid-based nanodrug delivery systems for the treatment of respiratory diseases where inhalation is the preferred route of administration.
摘要：
由于磷脂对大小有重要影响，脂质体的表面电势和硬度决定了它们吸入后的体内命运，本研究系统评价了磷脂对脂质体肺部给药的影响。在这项研究中,由中性饱和/不饱和磷脂组成的脂质体，构建了阴离子和阳离子磷脂，以研究表面电势和脂肪酸链的饱和度如何在体外和体内决定其粘液和上皮渗透性。我们的研究结果清楚地表明，由饱和中性和阴离子磷脂组成的脂质体具有很高的稳定性和渗透性，与由不饱和磷脂和阳离子磷脂组成的脂质体相比。此外，进行了荧光标记脂质体的体内成像和脂质体中包封的丹酚酸B(SAB)的生物分布,以评估磷脂对吸入脂质体的肺暴露和滞留的影响.最后,吸入SAB脂质体通过抑制炎症和调节凝血-纤溶系统,在博来霉素诱导的特发性肺纤维化小鼠模型中显示出增强的治疗效果.这些发现将有益于开发用于治疗呼吸道疾病的可吸入的基于脂质的纳米药物递送系统,其中吸入是优选的施用途径。
