Targeted Drug Delivery System for Pulmonary Fibrosis: Design and Development of Biomaterials

Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by excessive extracellular matrix deposition and tissue scarring, and leading to impaired lung function and respiratory failure. Although current treatments, such as pirfenidone and nintedanib, slow disease progression, they fail to completely halt or reverse fibrosis. Therefore, innovative therapeutic strategies are needed. Targeted drug delivery systems (TDDSs) are emerging as promising solutions. Biomaterials play critical roles in these systems by enhancing drug specificity, availability, and efficacy, while minimizing systemic toxicity. The most notable biomaterials include nanotechnology-based systems, including liposomes and polymeric nanoparticles, which facilitate drug penetration and slow release in fibrotic tissues. Hydrogels have three-dimensional structures providing controlled and sustained drug release at inflammation sites, and therefore are particularly valuable in PF treatment. Furthermore, biological carriers such as stem cells and extracellular vesicles have biocompatibility and anti-inflammatory effects that improve therapeutic outcomes. Despite the promising potential of these systems, clinical translation is hindered by several challenges, including immune clearance, stability of delivery platforms, and optimization of drug retention within diseased tissues. Interdisciplinary approaches integrating precision medicine with advancements in biomaterials may provide solutions opening new avenues for PF treatment. This review discusses current developments in targeted drug delivery for PF, emphasizing the importance of biomaterials, the mechanisms and barriers involved in pulmonary drug delivery, and future perspectives for overcoming current limitations. The ultimate goal is to improve patient outcomes by revolutionizing the approach to PF treatment through advanced drug delivery technologies.