Nanosuspensions-Based Dry Powder Inhalers for Pulmonary Delivery of Hydrophobic Natural Products: Formulation Strategies, Efficacy, and Challenges

Pulmonary delivery of nanosuspensions has emerged as a transformative strategy to enhance the bioavailability of hydrophobic natural products (HNPs) in the treatment of pulmonary infections and systemic diseases. However, challenges remain in balancing the safety and efficacy of nanosuspension-based inhalable formulations, particularly regarding formulation stability and lung deposition efficiency. This review systematically evaluates recent advancements in inhalable nanosuspension technologies, with a focus on dry powder inhaler (DPI) formulations tailored for HNPs (e.g., curcumin, resveratrol, breviscapine, paclitaxel). Key factors influencing formulation performance, including human lung anatomy, inflammatory microenvironments, fine particle index (FPI ≥ 50%), and physicochemical stability, are critically discussed. In vitro characterization (e.g., particle size of 1-5 μm, aerosolization efficiency >60%) and in vivo studies demonstrate that optimized nanosuspensions achieve 2-3-fold higher lung retention compared to conventional formulations, along with improved permeability across inflamed alveolar epithelia. Despite these advancements, challenges such as protein corona formation, batch-to-batch variability, and long-term storage stability call for further interdisciplinary innovation. This review highlights nanosuspensions as a transformative platform for the precision pulmonary delivery of HNPs, emphasizing the need for standardized characterization and translational validation to bridge the bench-to-bedside gap.