Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Guwahati, Assam 781101, India.
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research Guwahati, Assam 781101, India.
Int J Pharm. 2024 Dec 5;666:124745. doi: 10.1016/j.ijpharm.2024.124745. Epub 2024 Sep 23.
The higher incidence and mortality rate among all populations worldwide explains the unmet solutions in the treatment of lung cancer. The evolution of targeted therapies using tyrosine kinase inhibitors (TKI) has encouraged anticancer therapies. However, on-target and off-target effects and the development of drug resistance limited the anticancer potential of such targeted biologics. The advances in nanotechnology-driven-TKI embedded carriers that offered a new path toward lung cancer treatment. It is the inhalation route of administration known for its specific, precise, and efficient drug delivery to the lungs. The development of numerous TKI-nanocarriers through inhalation is proof of TKI growth. The future scopes involve using potential lung cancer biomarkers to achieve localized active cancer-targeting strategies. The adequate knowledge of in vitro absorption models usually helps establish better in vitro - in vivo correlation/extrapolation (IVIVC/E) to successfully evaluate inhalable drugs and drug products. The advanced in vitro and ex vivo lung tissue/ organ models offered better tumor heterogeneity, etiology, and microenvironment heterogeneity. The involvement of lung cancer organoids (LCOs), human organ chip models, and genetically modified mouse models (GEMMs) has resolved the challenges associated with conventional in vitro and in vivo models. To access potential inhalation-based drugtherapies, biological barriers, drug delivery, device-based challenges, and regulatory challenges must be encountered associated with their development. A proper understanding of material toxicity, size-based particle deposition at active disease sites, mucociliary clearance, phagocytosis, and the presence of enzymes and surfactants are required to achieve successful inhalational drug delivery (IDD). This article summarizes the future of lung cancer therapy using targeted drug-mediated inhalation using TKI.
在全球所有人群中，肺癌的发病率和死亡率都较高，这说明了在肺癌治疗方面尚未满足的需求。使用酪氨酸激酶抑制剂 (TKI) 的靶向治疗药物的发展促进了癌症治疗。然而，针对靶点和非靶点的作用以及耐药性的发展限制了这些靶向生物制剂的抗癌潜力。纳米技术驱动的 TKI 嵌入式载体的进步为肺癌治疗提供了新途径。这是一种众所周知的吸入给药途径，具有将药物特异性、精确地递送到肺部的优势。通过吸入开发了许多 TKI-纳米载体，证明了 TKI 的发展。未来的研究范围包括使用潜在的肺癌生物标志物来实现针对癌症的局部主动靶向策略。充分了解体外吸收模型通常有助于建立更好的体外-体内相关性/外推（IVIVC/E），以成功评估可吸入药物和药物产品。先进的体外和离体肺组织/器官模型提供了更好的肿瘤异质性、病因和微环境异质性。肺癌类器官（LCOs）、人体器官芯片模型和基因修饰小鼠模型（GEMMs）的参与解决了与传统体外和体内模型相关的挑战。为了获得潜在的基于吸入的药物治疗方法，必须克服与开发相关的生物屏障、药物输送、基于设备的挑战和监管挑战。为了实现成功的吸入式药物输送（IDD），需要充分了解材料毒性、在活性疾病部位基于大小的颗粒沉积、黏液纤毛清除、吞噬作用以及酶和表面活性剂的存在。本文总结了使用 TKI 进行靶向药物介导吸入治疗肺癌的未来。
