Customizable resveratrol spray-dried micro-composites for inhalation as a promising contender for treatment of idiopathic pulmonary fibrosis

The past decades have witnessed tremendous expansion in utilization of plant-derived medicines as resveratrol (RES) in treating several diseases like idiopathic pulmonary fibrosis (IPF). RES can exhibit its role in treating IPF via its outstanding antioxidant and anti-inflammatory activities. The goal of this work was to formulate RES-loaded spray-dried composite microparticles (SDCMs) suitable for pulmonary delivery via dry powder inhaler (DPI). They were prepared by spray drying of a previously prepared RES-loaded bovine serum albumin nanoparticles (BSA NPs) dispersion using different carriers. RES-loaded BSA NPs, prepared by the desolvation technique, acquired suitable particle size of 177.67 ± 0.95 nm and entrapment efficiency of 98.7 ± 0.35% with perfectly uniform size distribution and high stability. Considering the attributes of the pulmonary route, NPs were co-spray dried with compatible carriers viz. mannitol, dextran, trehalose, leucine, glycine, aspartic acid, and glutamic acid to fabricate SDCMs. All formulations showed suitable mass median aerodynamic diameter<5 µm; that is suitable for deep lung deposition. However, the best aerosolization behavior was attained from using leucine with fine particle fraction (FPF) of 75.74%, followed by glycine with FPF of 54.7%. Finally, a pharmacodynamic study was conducted on bleomycin-induced mice, and it strongly revealed the role of the optimized formulations in alleviating PF through suppressing the levels of hydroxyproline, tumor necrosis factor-α and matrix metalloproteinase-9 with obvious improvements in the treated lung histopathology. These findings indicate that in addition to leucine, the glycine amino acid, which is not commonly used yet, is very promising in the formulation of DPIs.