Deoxyribonuclease aerosols

Humidification of inspired air may promote the hydration (liquefaction) of tenacious secretions, allowing for more effective sputum production. The use of mucolytic aerosols (e.g., N-acetylcysteine deoxyribonuclease) is of questionable therapeutic value. Mucolytics may have the greatest benefit... 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Small amounts of surfactants may be used to prevent aggregation of proteins and may enhance the refolding process when the dried protein dissolves. Buffers may also help to prevent aggregation of the dissolved drug. Similarly, polymers may be used as aggregation inhibitors or to form matrices. Chan et al. [86] prepared crystalline powders of recombinant human deoxyribonuclease with high fractions of sodium chloride. These powders were formulated as adhesive mixtures on lactose and mannitol and showed improved aerosolization behaviour compared to the pure protein. 

Patients with cystic fibrosis use aerosol inhaler sprays of the DNA-hydrolyzing enzyme deoxyribonuclease to help reduce the viscosity of mucous secretions, which contain large amounts of DMA arising from destruction of WBCs as they fight lung Infections. 

Although there is still no cure for cystic fibrosis, several pharmacologic techniques have been recently developed that may help decrease the viscosity of respiratory secretions in patients with this disease. One technique uses aerosol preparations that contain enzymes known as deoxyribonucleases. These enzymes can be inhaled to break down the large quantities of DNA that are present in respiratory secretions of patients with cystic fibrosis.48,104 Respiratory secretions in these patients often contain large amounts of DNA because the genetic material contained in airway in-... 

Maa et al. [3.84] used spray drying and spray freeze-drying (see Chapter 5, [5.13, 5.14]) to produce protein powders for inhalation from deoxyribonuclease (rhDNase) and anti-IgE monoclonal antibody (anti-IgE Mab) with lactose as carrier. Spray freezedrying produced light and porous protein particles with superior aerosol performance. 

B. W. Ramsey, 8. J. Aslley, M. L. Ailken, W, Burke, A. A. Colin, H. L, Dorian, J. D. hisenbe, K. L. Gibson, I. R. Harwood, D. V. Schidlow, et al. Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis. Am. jfeu Reqtir. Dm, /4 ]45-l Jl (1993k... 

Chan, H.-K. Clark, A. Gonda, I. Mumenthaler, M. Hsu, C. Spray dried powders and powder blends of recombinant human deoxyribonuclease (rhDNase) for aerosol delivery. Pharm. Res. 1997, 14, 431-497. 

Cipolla, D.C. Clark, A.R. Chan, H.-K. Gonda, I. Shire, 59. S.J. Assessment of aerosol delivery systems for the recombinant human deoxyribonuclease I (rhDNase). STP Pharma Sciences 1994, 4, 50-62. 

Bustami RT, Chan HK, Sweeney T, Dehghani F, and Foster NR. Generation of Fine Powders of Recombinant Human Deoxyribonuclease using the Aerosol Solvent Extraction System. Pharmaceutical Research 2003 20 2028—2035. 

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