Chitosan-based binary dry powder inhaler carrier with nanometer roughness for improving in vitro and in vivo aerosolization performance.

Suitable nanometer roughness favors interactions between drugs and carriers, and it is a promising approach to enhance the aerosolization performance of carrier-based dry powder inhalers (DPIs). In this study, by altering the molecular migration rates, chitosan-based binary carriers (CBBCs) with nanometer roughness were fabricated for DPIs. Comprehensive physicochemical characterizations were conducted to elucidate the formation mechanism of the CBBCs. It was hypothesized that different constituent ratios in the formulations would result in different assembling of the particles and diverse roughness scales. The fine particle fractions (FPF, approximately 40~60%) of nanometer roughness CBBC-based DPI formulations were satisfactory, demonstrating the enhancement of the in vitro aerodynamic performance. The positive correlation (R2 = 0.9883) between the nanometer roughness and FPF was revealed, and the surface roughness of 20 nm might achieve the best aerosolization performance. CBBCs (optimal formulations) showed no difference in cytotoxicity on A549 and Calu-3 cells (p > 0.05). Additionally, the increased Cmax and AUC0-8h of the formulation with the nanometer roughness (p < 0.05) were observed in pharmacokinetic studies, which resulted from the improved in vivo aerosolization performance. In summary, the CBBCs were a prospective tool to improve the in vitro and in vivo aerosolization performance of DPIs. Graphical abstract ᅟ.