Nano-Formulations for Pulmonary Delivery: Past, Present, and Future Perspectives.

With the development of nanotechnology and confronting the problems of traditional pharmaceutical formulations in treating lung diseases, inhalable nano-formulations have attracted interest. Inhalable nano-formulations for treating lung diseases allow for precise pulmonary drug delivery, overcoming physiological barriers, improving aerosol lung deposition rates, and increasing drug bioavailability. They are expected to solve the difficulties faced in treating lung diseases. However, limited success has been recorded in the industrialization translation of inhalable nano-formulations. Only one relevant product has been approved by the FDA to date, suggesting that there are still many issues to be resolved in the clinical application of inhalable nano-formulations. These systems are characterized by a dependence on inhalation devices, while the adaptability of device formulation is still inconclusive, which is the most important issue impeding translational research. In this review, we categorized various inhalable nano-formulations, summarized the advantages of inhalable nano-formulations over conventional inhalation formulations, and listed the inhalable nano-formulations undergoing clinical studies. We focused on the influence of inhalation devices on nano-formulations and analyzed their adaptability. After extensive analysis of the drug delivery mechanisms, technical processes, and limitations of different inhalation devices, we concluded that vibrating mesh nebulizers might be most suitable for delivering inhalable nano-formulations, and related examples were introduced to validate our view. Finally, we presented the challenges and outlook for future development. We anticipate providing an informative reference for the field.