Wyszogrodzka-Gaweł Gabriela, Stróżyk Maciej, Skoda Marta, Osial Magdalena, Baran Ewelina, Mendyk Aleksander
Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland.
Nanotechnol Sci Appl. 2025 Sep 22;18:405-421. doi: 10.2147/NSA.S539424. eCollection 2025.
This review explores the emerging potential of theranostic approaches in the pulmonary delivery of antimicrobial agents, with particular attention to recent FDA warnings concerning inhaled antifungal therapies. Pulmonary infections remain difficult to treat effectively due to the limitations of systemic drug delivery, anatomical and physiological barriers within the lungs, and microbial strategies that promote colonization. Inhaled drug delivery offers a targeted alternative but faces significant challenges, including the inherent variability of lung anatomy, disease-induced pulmonary alterations, and host defence mechanisms. We examine the crucial role of lung imaging in enabling theranostic applications, emphasizing magnetic resonance imaging (MRI) as the most promising modality due to its ability to provide non-invasive, radiation-free, and repeatable assessments of drug deposition. Within this context, the use of superparamagnetic iron oxide nanoparticles (SPIONs) as MRI contrast agents is critically assessed. SPIONs offer a safer alternative to gadolinium-based agents and hold considerable promise for improving the precision of imaging and treatment monitoring in the lungs. The article also outlines the significant regulatory barriers to the development and clinical adoption of inhaled antimicrobial therapies. These include the lack of standardized patient selection criteria, poorly defined clinical endpoints, and the inherent complexity of trial design for heterogeneous patient populations. To address these issues, we propose a conceptual framework for translating inhaled theranostic formulations into personalized antimicrobial therapies. This includes individualized dose adjustments based on imaging data and real-time monitoring of drug concentrations at the infection site. Such a tailored approach could significantly enhance treatment outcomes and meet the urgent clinical need for safer, more effective inhaled antimicrobial treatments.
本综述探讨了治疗诊断方法在肺部递送抗菌药物方面新出现的潜力，尤其关注美国食品药品监督管理局（FDA）最近关于吸入性抗真菌治疗的警告。由于全身给药的局限性、肺部的解剖和生理屏障以及促进定植的微生物策略，肺部感染仍然难以有效治疗。吸入给药提供了一种有针对性的替代方法，但面临重大挑战，包括肺部解剖结构的固有变异性、疾病引起的肺部改变以及宿主防御机制。我们研究了肺部成像在实现治疗诊断应用中的关键作用，强调磁共振成像（MRI）是最有前景的方式，因为它能够对药物沉积进行无创、无辐射且可重复的评估。在此背景下，对超顺磁性氧化铁纳米颗粒（SPIONs）作为MRI造影剂的应用进行了严格评估。与钆基造影剂相比，SPIONs提供了一种更安全的选择，在提高肺部成像和治疗监测的精度方面具有很大潜力。本文还概述了吸入性抗菌治疗开发和临床应用面临的重大监管障碍。这些障碍包括缺乏标准化的患者选择标准、定义不明确的临床终点以及针对异质患者群体的试验设计的固有复杂性。为解决这些问题，我们提出了一个将吸入性治疗诊断制剂转化为个性化抗菌治疗的概念框架。这包括根据成像数据进行个体化剂量调整以及对感染部位药物浓度进行实时监测。这种量身定制的方法可以显著提高治疗效果，并满足对更安全、更有效的吸入性抗菌治疗的迫切临床需求。
