Pal Ravi Raj, Rajpal Vasundhara, Singh Priya, Saraf Shubhini A
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), VidyaVihar, Raebareli Road, Lucknow 226025, Uttar Pradesh, India.
Department of Biotechology, Babasaheb Bhimrao Ambedkar University (A Central University), VidyaVihar, Raebareli Road, Lucknow 226025, Uttar Pradesh, India.
Pharmaceutics. 2021 May 22;13(6):775. doi: 10.3390/pharmaceutics13060775.
Cancer causes a considerable amount of mortality in the world, while arthritis is an immunological dysregulation with multifactorial pathogenesis including genetic and environmental defects. Both conditions have inflammation as a part of their pathogenesis. Resistance to anticancer and disease-modifying antirheumatic drugs (DMARDs) happens frequently through the generation of energy-dependent transporters, which lead to the expulsion of cellular drug contents. Thymoquinone (TQ) is a bioactive molecule with anticancer as well as anti-inflammatory activities via the downregulation of several chemokines and cytokines. Nevertheless, the pharmacological importance and therapeutic feasibility of thymoquinone are underutilized due to intrinsic pharmacokinetics, including short half-life, inadequate biological stability, poor aqueous solubility, and low bioavailability. Owing to these pharmacokinetic limitations of TQ, nanoformulations have gained remarkable attention in recent years. Therefore, this compilation intends to critically analyze recent advancements in rheumatoid arthritis and cancer delivery of TQ. This literature search revealed that nanocarriers exhibit potential results in achieving targetability, maximizing drug internalization, as well as enhancing the anti-inflammatory and anticancer efficacy of TQ. Additionally, TQ-NPs (thymoquinone nanoparticles) as a therapeutic payload modulated autophagy as well as enhanced the potential of other drugs when given in combination. Moreover, nanoformulations improved pharmacokinetics, drug deposition, using EPR (enhanced permeability and retention) and receptor-mediated delivery, and enhanced anti-inflammatory and anticancer properties. TQ's potential to reduce metal toxicity, its clinical trials and patents have also been discussed.
癌症在全球造成了相当高的死亡率，而关节炎是一种免疫调节失调，其发病机制具有多因素性，包括遗传和环境缺陷。这两种病症的发病机制都包含炎症。对抗癌药物和改善病情的抗风湿药物（DMARDs）的耐药性经常通过能量依赖性转运蛋白的产生而发生，这会导致细胞内药物成分的排出。百里醌（TQ）是一种生物活性分子，通过下调多种趋化因子和细胞因子，具有抗癌和抗炎活性。然而，由于其内在的药代动力学特性，包括半衰期短、生物稳定性不足、水溶性差和生物利用度低，百里醌的药理学重要性和治疗可行性未得到充分利用。由于TQ存在这些药代动力学限制，纳米制剂近年来受到了显著关注。因此，本综述旨在批判性地分析百里醌在类风湿性关节炎和癌症治疗方面的最新进展。该文献检索表明，纳米载体在实现靶向性、最大化药物内化以及增强TQ的抗炎和抗癌疗效方面显示出潜在效果。此外，作为治疗载荷的TQ纳米颗粒（TQ-NPs）可调节自噬，并在联合使用时增强其他药物的潜力。此外，纳米制剂改善了药代动力学、药物沉积，利用了增强的通透性和滞留效应（EPR）以及受体介导的递送，并增强了抗炎和抗癌特性。还讨论了TQ降低金属毒性的潜力、其临床试验和专利情况。
