Evaluation of nose-only aerosol inhalation chamber and comparison of experimental results with mathematical simulation of aerosol deposition in mouse lungs

In vivo small rodent efficacy testing of new synthetic and biological molecules for the pulmonary route requires an efficient delivery device. For this purpose, a nose-only inhalation chamber was used to deliver aerosolized aqueous compounds to the respiratory tract of mice. The aim of the study was to determine the efficiency of dose delivery and deposition in the lungs of the mice using this chamber. A secondary goal was to compare the experimental lung deposition results with values predicted from mathematical simulation. Experimental tests were conducted by generating aerosols of a radiolabeled formulation of human serum albumin (HSA) with a mass median aerodynamic diameter (MMAD) of 3.9 +/- 0.5 mum and a geometric standard deviation (GSD) of 1.43 +/- 0.05 using PARI LC STAR jet nebulizers. Based on the total activity placed in the nebulizer, the chamber delivered 0.108 +/- 10.027% to the mice and 0.0087 +/- 0.0021% to the lungs of the mice. In vivo lung deposition was found to be 8.19 +/- 3.56% of total activity deposited in the mouse. Mathematical simulation predictions ranged between 5.89 and 4.40% for various breathing patterns, and did not differ significantly from the in vivo results (p > 0.10). These results provide important quantitative information relevant to aerosol delivery experiments in mouse models. Our results also suggest that the nose-only inhalation chamber would benefit from significant changes to increase the efficiency of deposition in mice such that it can be used for nebulization of expensive therapeutic drugs. (C) 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association.