申请人:THE UNIVERSITY OF BRITISH COLUMBIA
公开号:US20180221279A1
公开(公告)日:2018-08-09
Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.
本文提供了适用于装载到脂质体纳米粒载体中的药物衍生物。在一些首选方面,这些衍生物包括一种水溶性较差的药物衍生物,其与一种弱碱基团衍生化,有助于通过LN跨膜pH或离子梯度将药物活性地装载到LN的水相内部。弱碱基团可以选择性地包括一个亲脂性结构域,有助于将药物活性地装载到脂质体膜的内单分子层。优点是,药物衍生物的LN配方相对于相应的游离药物表现出改善的溶解度、降低的毒性、增强的疗效和/或其他优点。