Department of Pharmaceutics, Institute of Pharmacy, Nirma University, SG Highway, Chharodi, Ahmedabad 382481, Gujarat, India.
Department of Pharmaceutics, Institute of Pharmacy, Nirma University, SG Highway, Chharodi, Ahmedabad 382481, Gujarat, India.
J Control Release. 2019 May 10;301:76-109. doi: 10.1016/j.jconrel.2019.03.015. Epub 2019 Mar 16.
Employing combination therapy has become obligatory in cancer cases exhibiting high tumor load, chemoresistant tumor population, and advanced disease stages. Realization of this fact has now led many of the combination oncotherapies to become an integral part of anticancer regimens. Combination oncotherapy may encompass a combination of anticancer agents belonging to a similar therapeutic category or that of different therapeutic categories (e.g. chemotherapy + gene therapy). Differences in the physicochemical properties, pharmacokinetics and biodistribution pattern of different payloads are the major constraints that are faced by combination chemotherapy. Concordant efforts in the field of nanotechnology and oncology have emerged with several approaches to solve the major issues encountered by combination therapy. Unique colloidal behaviors of various types of nanoparticles and differential targeting strategies have accorded an unprecedented ability to optimize combination oncotherapeutic delivery. Nanocarrier based delivery of the various types of payloads such as chemotherapeutic agents and other anticancer therapeutics such as small interfering ribonucleic acid (siRNA), chemosensitizers, radiosensitizers, and antiangiogenic agents have been addressed in the present review. Various nano-delivery systems like liposomes, polymeric nanoparticles, polymerosomes, dendrimers, micelles, lipid based nanoparticles, prodrug based nanocarriers, polymer-drug conjugates, polymer-lipid hybrid nanoparticles, carbon nanotubes, nanosponges, supramolecular nanocarriers and inorganic nanoparticles (gold nanoparticles, silver nanoparticles, magnetic nanoparticles and mesoporous silica based nanoparticles) that have been extensively explored for the formulation of multidrug delivery is an imperative part of discussion in the review. The present review features the outweighing benefits of combination therapy over mono-oncotherapy and discusses several existent nanoformulation strategies that facilitate a successful combination oncotherapy. Several obstacles that may impede in transforming nanotechnology-based combination oncotherapy from bench to bedside, and challenges associated therein have also been discussed in the present review.
在肿瘤负荷高、化疗耐药肿瘤人群和晚期疾病阶段的癌症病例中，采用联合治疗已成为必要。这一事实的认识现在导致许多联合肿瘤治疗成为癌症治疗方案的一个组成部分。联合肿瘤治疗可能包括属于相似治疗类别的抗癌药物的联合，或属于不同治疗类别的抗癌药物的联合（例如化疗+基因治疗）。不同有效载荷的物理化学性质、药代动力学和生物分布模式的差异是联合化疗面临的主要限制。纳米技术和肿瘤学领域的协同努力已经出现了几种方法来解决联合治疗中遇到的主要问题。各种类型的纳米粒子的独特胶体行为和差异化靶向策略为优化联合肿瘤治疗药物的传递提供了前所未有的能力。本综述中讨论了基于纳米载体的各种有效载荷的递药，如化疗药物和其他抗癌治疗药物，如小干扰核糖核酸（siRNA）、化疗增敏剂、放射增敏剂和抗血管生成剂。各种纳米递药系统，如脂质体、聚合物纳米粒子、聚合物体、树枝状大分子、胶束、基于脂质的纳米粒子、前药纳米载体、聚合物-药物偶联物、聚合物-脂质杂化纳米粒子、碳纳米管、纳米海绵、超分子纳米载体和无机纳米粒子（金纳米粒子、银纳米粒子、磁性纳米粒子和介孔硅基纳米粒子）已被广泛探索用于多药递药的制剂，是本综述讨论的一个重要部分。本综述强调了联合治疗相对于单药治疗的优势，并讨论了几种现有的纳米制剂策略，这些策略有助于成功的联合肿瘤治疗。本综述还讨论了可能阻碍基于纳米技术的联合肿瘤治疗从实验室到临床的几个障碍，以及其中存在的挑战。
