Drug derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drug derivatized with a weak-base moiety that facilitates active loading of the drug 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 drug to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drug derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drugs.
本文提供了适合装载到脂质体纳米粒子载体中的药物衍
生物。在一些首选方面,这些衍
生物包括一个
水溶性较差的药物,经过衍生化处理得到一个弱碱基团,该碱基团通过LN跨膜pH或离子梯度促进药物的主动装载到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,该结构域促进药物主动装载到脂质体膜的内单层。有利的是,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。