Inhaled lung cancer therapy is promising because of direct and noninvasive drug delivery to the lungs with low potential for severe systemic toxicity. Thus chemotherapeutic drugs have been administered clinically by nebulization of solution or suspension formulations, which demonstrated their limited pulmonary absorption and relatively mild systemic toxicity. In all these clinical trials, however, there was no obviously superior anticancer efficacy in lung cancer patients even at the maximum doses of drugs limited by pulmonary toxicity. Therefore methods that deliver both higher anticancer efficacy and lower pulmonary toxicity are strongly desired. In addition to the worldwide availability of pressured metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) to treat local respiratory diseases, recent innovations in medicines and technologies are encouraging next steps toward effective inhaled lung cancer therapy with new therapeutic or drug delivery concepts. These include the discovery of target cells/molecules and drug candidates for novel cancer therapy, the development of high-performance inhalation devices for effective pulmonary drug delivery, and the establishment of manufacturing technologies for functional nanoparticles/microparticles. This review highlights the present situation and future progress of inhaled drugs for lung cancer therapy, including an overview of available inhalation devices, pharmacokinetics, and outcomes in clinical trials so far and some novel formulation strategies based on drug delivery systems to achieve enhanced anticancer efficacy and attenuated pulmonary toxicity.

中文翻译：

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吸入式肺癌治疗的现状和未来进展：具有药物输送功能的吸入制剂的必要性。

吸入式肺癌治疗前景广阔，因为它直接和无创地将药物输送到肺部，严重的全身毒性反应可能性很小。因此，化学疗法药物已经通过溶液或悬浮液制剂的雾化而在临床上施用，这证明了它们的有限的肺吸收和相对轻度的全身毒性。然而，在所有这些临床试验中，即使在最大剂量的受肺毒性限制的药物中，肺癌患者也没有明显优越的抗癌功效。因此，强烈期望提供更高的抗癌功效和更低的肺毒性的方法。除了在全球范围内可以使用压力计量吸入器（pMDI）和干粉吸入器（DPI）来治疗局部呼吸道疾病外，最近在药物和技术方面的创新正在鼓励通过新的治疗或药物递送概念朝着有效的吸入性肺癌治疗迈出下一步。这些措施包括发现用于新型癌症治疗的靶细胞/分子和候选药物，开发用于有效肺部药物递送的高性能吸入装置以及建立功能性纳米颗粒/微粒的制造技术。这篇综述着重介绍了用于肺癌治疗的吸入药物的现状和未来进展，包括迄今为止可用的吸入装置，药代动力学和临床试验结果的概述，以及基于药物递送系统的新型制剂策略，以实现增强的抗癌功效和减弱的肺毒性。