Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai - 400085, India.
Homi Bhabha National Institute, Anushaktinagar, Mumbai - 400 094, India.
Curr Pharm Des. 2019;25(28):3034-3056. doi: 10.2174/1381612825666190830155319.
Cancer is the major public health problem in developing countries. The treatment of cancer requires a multimodal approach and chemotherapy is one of them. Chemotherapeutic drug is administered to cancer patients in the form of a formulation which is prepared by mixing an active ingredient (drug) with the excipient. The role of excipient in a formulation is to regulate the release, bio-distribution, and selectivity of drug within the body.
In this context, selectivity of an anticancer formulation is achieved through two mechanisms like passive and active targeting. The passive targeting of a formulation is generally through enhanced permeation retention (EPR) effect which is dictated by physical properties of the carrier such as shape and size. On the contrary, active targeting means surface functionalization of excipient with target-specific ligands and/or receptors to increase its selectivity.
Over the past several decades, remarkable progress has been made in the development and application of an engineered excipient or carrier to treat cancer more effectively. Especially nanoparticulate systems composed of metal/liposomes/polymeric material/proteins have received significant attention in the rational design of anticancer drug formulations; for example, therapeutic agents have been integrated with nanoparticles of optimal sizes, shapes and surface properties to improve their solubility, circulation half-life, and bio-distribution. In this review article, recent literature is included to discuss the role of physicochemical properties of excipients in achieving tumour targeting through passive and active approaches.
The selection of an excipient/carrier and targeting ligand plays a very important role in rational design and development of anticancer drug formulations.
癌症是发展中国家的主要公共卫生问题。癌症的治疗需要采用多模式方法,化疗就是其中之一。化疗药物以制剂的形式施用于癌症患者,该制剂是通过将活性成分(药物)与赋形剂混合制备而成。赋形剂在制剂中的作用是调节药物在体内的释放、生物分布和选择性。
在这种情况下,通过被动和主动靶向两种机制来实现抗癌制剂的选择性。制剂的被动靶向通常是通过增强渗透保留(EPR)效应来实现的,EPR 效应由载体的物理性质(如形状和大小)决定。相反,主动靶向是指通过将靶向配体和/或受体表面功能化来增加赋形剂的选择性。
在过去的几十年中,在开发和应用工程化赋形剂或载体以更有效地治疗癌症方面取得了显著进展。特别是由金属/脂质体/聚合物材料/蛋白质组成的纳米颗粒系统在抗癌药物制剂的合理设计中受到了极大关注;例如,已经将治疗剂与最佳尺寸、形状和表面特性的纳米颗粒结合起来,以提高其溶解度、循环半衰期和生物分布。在这篇综述文章中,纳入了最近的文献来讨论赋形剂的物理化学性质在通过被动和主动方法实现肿瘤靶向中的作用。
赋形剂/载体和靶向配体的选择在抗癌药物制剂的合理设计和开发中起着非常重要的作用。