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.

Objective: The objective of this study was to explore the possibility of treating heart failure in rats by delivering mRNA of 24-dehydrocholesterol reductase (DHCR24) into the body through lipid nanoparticles (LNPs). Methods: We established a heart failure rat model using doxorubicin. The experiment was divided into blank, model, mRNA stock solution cardiac injection, mRNA stock solution intravenous injection, LNP-mRNA stock solution cardiac injection, and LNP-mRNA stock solution intravenous injection groups. We directly injected DHCR24-mRNA or LNP-DHCR24-mRNA into the myocardium in three regions through an insulin needle passing through the intercostal space under the guidance of B-ultrasound. We recorded the mortality rate, body weight, 6-min walk test return times, and organ weight of rats after administration and detected the cardiac structure and function using B-ultrasound and transmission electron microscopy (TEM). Additionally, we tested for HE staining; PRDX2, Sirt3, and TRX1 protein expression; and IL-1 β, IL-10, VEGF, NT proBNP, and BNP cytokine concentrations. Results: Compared with the model group, the administration of DHCR24-mRNA significantly reduced mortality; decreased weight loss, the ratio of heart to tibia length, and spleen weight; and improved rat motility. The administration of DHCR24-mRNA can postpone the pathological morphological alterations of myocardial cells and reduce inflammatory infiltration. In terms of biochemistry, the administration of DHCR24-mRNA can increase the expression of the PRDX2, Sirt3, and TRX1 proteins; increase the concentrations of IL-10 and VEGF; and reduce the concentrations of IL-1β, NT proBNP, and BNP. The administration of DHCR24-mRNA can also delay the process of heart failure. The delivery and therapeutic effect of DHCR24-mRNA encapsulated in LNPs were better when compared to the other groups. Conclusions: DHCR24-mRNA encapsulated in LNPs can be effectively administered to rats with heart failure and exhibits some curative effects.