Aerosol Delivery of Dornase Alfa Generated by Jet and Mesh Nebulizers.

Kyung Hwa Chang,Bong Joo Park,Sun Kook Yoo,Ki Chang Nam,Sang-Hyub Moon

doi:10.3390/pharmaceutics12080721

Kyung Hwa Chang, Bong Joo Park + Show 3 more

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https://doi.org/10.3390/pharmaceutics12080721

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Abstract

Recent reports on mesh nebulizers suggest the possibility of stable nebulization of various therapeutic protein drugs. In this study, the in vitro performance and drug stability of jet and mesh nebulizers were examined for dornase alfa and compared with respect to their lung delivery efficiency in BALB/c mice. We compared four nebulizers: two jet nebulizers (PARI BOY SX with red and blue nozzles), a static mesh nebulizer (NE-U150), and a vibrating mesh nebulizer (NE-SM1). The enzymatic activity of dornase alfa was assessed using a kinetic fluorometric DNase activity assay. Both jet nebulizers had large residual volumes between 24% and 27%, while the volume of the NE-SM1 nebulizer was less than 2%. Evaluation of dornase alfa aerosols produced by the four nebulizers showed no overall loss of enzymatic activity or protein content and no increase in aggregation or degradation. The amount of dornase alfa delivered to the lungs was highest for the PARI BOY SX-red jet nebulizer. This result confirmed that aerosol droplet size is an important factor in determining the efficiency of dornase alfa delivery to the lungs. Further clinical studies and analysis are required before any conclusions can be drawn regarding the clinical safety and efficacy of these nebulizers.

Highlights

Dornase alfa is a highly purified solution of recombinant human pancreatic deoxyribonuclease I, an enzyme that selectively cleaves DNA
The output rates of dornase alfa for the JN-PARIr, JN-PARIb, SMN-U150, and VMN-SM1 nebulizers were 0.140 ± 0.002, 0.170 ± 0.004, 0.311 ± 0.002, and 0.238 ± 0.002 min charged volume (mL)/min, respectively: the same order as that observed for aerosol droplet sizes (Table 3). These results show that the mesh nebulizers had smaller residual volumes and shorter nebulization times than the jet nebulizers
Our results showed no overall loss of enzymatic activity or protein content and no increase in aggregation or degradation following aerosolization by the four studied nebulizers

Summary

Introduction

Dornase alfa (proprietary name: Pulmozyme, from Genentech) is a highly purified solution of recombinant human pancreatic deoxyribonuclease I (rhDNase I), an enzyme that selectively cleaves DNA. The long-term effects of dornase alfa on lung exacerbation and its short-term (not more than 14 d) and long-term effects on lung function have been studied in clinical trials. These trials showed that dornase alfa is well tolerated, significantly improves lung function, and reduces the risk of pulmonary exacerbations [2,3,4,5,6,7,8,9]. According to the guidelines issued for chronic respiratory medication in CF patients, chronic patients aged over 6 years should inhale a 2.5 mg single-use ampule once daily using a recommended nebulizer [10]

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