Method for Pulmonary Administration Using Negative Pressure Generated by Inspiration in Mice

Abstract

When developing inhaled medicines for respiratory diseases, such as chronic obstructive pulmonary disease, drugs need to be administered by pulmonary delivery to animals in non-clinical tests. Common methods require application of pressure during administration, and it may cause lung injury, so we focused on the inhalation of liquid medicines by mice themselves. This study aimed to evaluate a negative pressure method of pulmonary administration in mice by self-inhalation. First, to confirm the accuracy of delivery of liquid medicines into lungs and the potential for lung injury, Institute of Cancer Research (ICR) mice received methylene blue tetrahydrate or saline by the negative pressure method. We assessed drug distribution and usefulness of this method by administering porcine pancreatic elastase and all-trans-retinoic acid (ATRA) to mice. Consequently, we confirmed good distribution of the dye and no injury such as disruption of blood flow or destruction of alveoli in lungs of mice. Following production of the murine emphysema model, the mean linear intercept (Lm) was calculated as 78 ± 4 μm. Moreover, a significant therapeutic effect of administration of the ATRA was confirmed. These results suggest that this negative pressure method of administration may be useful for pulmonary administration in non-clinical tests.