Özge Özgenç Çınar, Ilgin Kimiz‐Gebologlu, Suphi Ş. Öncel
INTRODUCTION: Collectively, these examples underscore that nanotechnology-based systems hold great promise for overcoming the intrinsic barriers of conventional therapies by achieving site-specific, sustained, and safer drug delivery in respiratory diseases. CONCLUSION: Nanoparticle-based drug delivery systems provide a significant advancement in the treatment of respiratory diseases by overcoming the fundamental limitations of conventional therapies. Through their small size, tunable physicochemical properties, and ability to target specific lung regions, nanoparticles ensure improved bioavailability, controlled release, and reduced systemic toxicity. Studies on various nanocarriers -such as ROS-responsive and GSH-triggered nanoparticles, nanoliposomal salbutamol sulfate, PLA nanoparticles, and mannose-conjugated chitosan nanoparticles- have demonstrated promising outcomes in enhancing drug retention, reducing inflammation, and improving therapeutic efficacy in respiratory disorders. Despite these achievements, challenges such as mucus barrier penetration, long-term pulmonary toxicity, and large-scale reproducibility still remain. However, ongoing interdisciplinary research combining materials science, pharmacology, and pulmonary biology continues to improve the design, safety, and performance of nanoparticle systems. Collectively, these advancements indicate that nanotechnology can transform the current therapeutic landscape of respiratory medicine, making treatments more effective, safer, and more patient-centered. Future Perspectives: The future of nanoparticle-based pulmonary therapies lies in the development of next-generation smart and personalized nanomedicines. Stimuli-responsive nanoparticles capable of detecting disease-specific microenvironments, such as pH shifts, oxidative stress, or enzymatic activity, will enable localized and on-demand drug release, minimizing off-target effects. Personalized nanomedicine approaches will allow the design of patient-specific formulations that combine multiple therapeutic agents, offering synergistic efficacy for complex respiratory disorders. Hybrid nanoplatforms that integrate metallic nanoparticles (e.g., silver, gold) with natural bioactive compounds such as phycocyanin are expected to exhibit both therapeutic and diagnostic potential, enhancing the scope of precision medicine. Furthermore, advancements in inhalation device technology, aerosol engineering, and biocompatible excipient development will further support the translation of nanoparticle-based formulations from laboratory research to clinical application. As large-scale production, regulatory harmonization, and long-term safety validation advance, nanoparticle-based systems are expected to become a cornerstone of future respiratory therapies, offering precision, safety, and efficacy beyond the limitations of current treatments.