Neuroscience Institute & Center for Behavioral Neuroscience, Georgia State University, 789 Petit Science Center, Atlanta, GA, 30303, United States.
Department of Computer Science, Georgia State University, 34 Peachtree Street, Atlanta, GA, 30303, United States; Department of Biology, Georgia State University, 34 Peachtree Street, Atlanta, GA, 30303, United States.
Pharmacol Res. 2019 Jan;139:91-105. doi: 10.1016/j.phrs.2018.11.005. Epub 2018 Nov 5.
A huge surge of research is being conducted on combination therapy with anticancer compounds formulated in the form of nanoparticles (NPs). Numerous advantages like dose minimalization and synergism, reversal of multi drug resistance (MDRs), enhanced efficacy have emerged with nanoencapsulation of chemotherapeutic agents with chemo-sensitizing agent like curcumin. Within last couple of years various nano-sized formulations have been designed and tested both in vitro with cell lines for different types of cancers and in vivo with cancer types and drug resistance models. Despite the combinatorial models being advanced, translation to human trials has not been as smooth as one would have hoped, with as few as twenty ongoing clinical trials with curcumin combination, with less than 1/10th being nano-particulate formulations. Mass production of nano-formulation based on their physico-chemical and pharmacokinetics deficits poses as major hurdle up the ladder. Combination of these nano-sized dosage with poorly bioavailable drugs, unspecific target binding ability and naturally unstable curcumin further complicates the formulation aspects. Emphasis is now therefore being laid on altering natural forms of curcumin and usage of formulations like prodrug or coating of curcumin to overcome stability issues and focus more on enhancing the pharmaceutical and therapeutic ability of the nano-composites. Current studies and futuristic outlook in this direction are discussed in the review, which can serve as the basis for upcoming research which could boost commercial translational of improved nano-sized curcumin combination chemotherapy.
大量研究正在进行，将抗癌化合物制成纳米粒子（NPs）的形式进行联合治疗。通过将化疗药物与姜黄素等化疗增敏剂纳米封装，出现了剂量最小化和协同作用、逆转多药耐药（MDRs）、增强疗效等诸多优势。在过去的几年中，已经设计并测试了各种纳米尺寸的制剂，包括不同类型癌症的细胞系中的体外和癌症类型和耐药模型中的体内。尽管组合模型得到了发展，但向人体试验的转化并不像人们希望的那样顺利，只有不到 20 项正在进行的姜黄素联合临床试验，其中不到 1/10 是纳米颗粒制剂。基于其物理化学和药代动力学缺陷的纳米制剂的大规模生产是一个主要障碍。这些纳米剂量与生物利用度差的药物、非特异性靶标结合能力和自然不稳定的姜黄素的组合进一步使制剂复杂化。因此，现在的重点是改变姜黄素的天然形式，并使用前药或姜黄素涂层等制剂来克服稳定性问题，更多地关注增强纳米复合材料的药物和治疗能力。本综述讨论了这一方向的当前研究和未来展望，可为即将进行的研究提供基础，从而促进改进的纳米姜黄素联合化疗的商业转化。
