Lee Michael S, Dees E Claire, Wang Andrew Z
Oncology (Williston Park). 2017 Mar 15;31(3):198-208.
Cytotoxic chemotherapies have a narrow therapeutic window, with high peaks and troughs of plasma concentration. Novel nanoparticle formulations of cytotoxic chemotherapy drugs can enhance pharmacokinetic characteristics and facilitate passive targeting of drugs to tumors via the enhanced permeability and retention effect, thus mitigating toxicity. Nanoparticle vehicles currently in clinical use or undergoing clinical investigation for anticancer therapies include liposomes, polymeric micelles, protein-drug nanoparticles, and dendrimers. Multiple nanoparticle formulations of existing cytotoxic chemotherapies are approved for use in several indications, with clinical data indeed showing optimization of pharmacokinetics and different toxicity profiles compared with their parent drugs. There are also many new nanoparticle drug formulations in development and undergoing early- and late-phase clinical trials, including several that utilize active targeting or triggered release based on environmental stimuli. Here, we review the rationale for nanoparticle formulations of existing or previously investigated cytotoxic drugs, describe currently approved nanoparticle formulations of drugs, and discuss some of the most promising clinical trials currently underway.
细胞毒性化疗药物的治疗窗较窄，血浆浓度存在高峰和低谷。细胞毒性化疗药物的新型纳米颗粒制剂可增强药代动力学特性，并通过增强的渗透和滞留效应促进药物被动靶向肿瘤，从而减轻毒性。目前正在临床使用或正在进行抗癌治疗临床研究的纳米颗粒载体包括脂质体、聚合物胶束、蛋白质 - 药物纳米颗粒和树枝状大分子。现有细胞毒性化疗药物的多种纳米颗粒制剂已获批用于多种适应症，临床数据确实显示与它们的母体药物相比，药代动力学得到优化，毒性特征也有所不同。此外，还有许多新的纳米颗粒药物制剂正在研发中，并正在进行早期和晚期临床试验，其中包括一些利用主动靶向或基于环境刺激的触发释放的制剂。在此，我们综述现有或先前研究的细胞毒性药物纳米颗粒制剂的基本原理，描述目前已获批的药物纳米颗粒制剂，并讨论一些目前正在进行的最有前景的临床试验。
