DDS Research, Global Formulation Research Japan, Pharmaceutical Science & Technology Core Function Unit, Eisai Product Creation Systems, Eisai Co, Ltd, Ibaraki 300–2635, Japan.
Biol Pharm Bull. 2013;36(5):703-7. doi: 10.1248/bpb.b12-01106.
Liposomes are drug delivery systems that can alter the pharmacokinetic properties of compounds. The adverse effects of anticancer agents are a limiting factor for cancer chemotherapy, therefore, liposomal formulations have the potential to improve the therapeutic efficacy of anticancer agents by enhancing their accumulation in tumors and reducing non-selective distribution to normal tissues, which is known as the enhanced permeability and retention effect. To develop a liposomal anticancer agent as a drug product, its formulation must be designed to ensure its quality until it is administered to patients and to exert maximum potency in clinical use rather than in animal experiments. The chemical stability and physicochemical stability of the ingredients are key factors in the design of liposomal formulations. Drug release rates are critical factors in the therapeutic efficacy of liposomal drug products because the encapsulated drug has no pharmacological activity, and only released drug can exert antitumor/toxic activities. Liposomes should maintain the drug in a stable state in the circulation and then promptly release it after accumulation in the target tissue in order to achieve a sufficient drug concentration. To understand the profile of the formulation and to guarantee the quality of drug product, a reliable analytical method that can determine the released and encapsulated drugs in biological fluids is required. Simple online solid phase extractions of the released and encapsulated drugs using a column-switching HPLC system meet the requirements and this system enables accurate in vitro release testing and in vivo pharmacokinetic evaluation. This review introduces the process of liposomal drug product development from various viewpoints.
脂质体是一种药物递送系统，可以改变化合物的药代动力学性质。抗癌药物的不良反应是癌症化疗的一个限制因素，因此，脂质体制剂有可能通过增强其在肿瘤中的积累并减少对正常组织的非选择性分布来提高抗癌药物的治疗效果，这被称为增强的通透性和保留效应。为了将脂质体抗癌药物开发为药物产品，其制剂必须设计为确保其质量，直到将其施用于患者，并在临床使用中发挥最大效力，而不是在动物实验中。化学稳定性和物理化学稳定性是脂质体制剂设计的关键因素。药物释放速率是脂质体药物产品治疗效果的关键因素，因为包封的药物没有药理活性，只有释放的药物才能发挥抗肿瘤/毒性作用。脂质体应在循环中使药物保持稳定状态，然后在积聚到靶组织后迅速释放，以达到足够的药物浓度。为了了解制剂的概况并保证药物产品的质量，需要一种能够在生物流体中测定释放和包封药物的可靠分析方法。使用柱切换 HPLC 系统对释放和包封药物进行简单的在线固相萃取符合要求，该系统能够进行准确的体外释放测试和体内药代动力学评估。这篇综述从多个角度介绍了脂质体药物产品的开发过程。
