DNAse, aerosolized

Intrarespiratory Aerosols DNAse delivered to lungs to rednce mucus accumulation... 

A small number of biopharmaceuticals are delivered by nonparenteral means. Recombinant DNase is given by inhalation aerosol to reduce the viscosity of mucus in the lungs of patients with cystic hbrosis. A platelet-derived growth factor in the form of a gel is administered topically for wound healing. Several hormones and peptides are administered in solution by the intranasal route. A solution of an antisense drug used for the treatment of cytomegalovirus retinitis is injected directly into the eye. 

Retention of viscous purulent secretions, which contain high concentrations of extracellular DNA—released by degenerating leukocytes that accumulate in response to infection [24]—in the airways contributes both to reduced pulmonary function and to exacerbations of infection [24,25], Digestion of DNA polymers in purulent secretion with DNAse (dornase-a or Pulmozyme) has been shown to reduce sputum viscosity in cystic fibrosis patients. The availability of recombinant DNAse has allowed its use in an aerosol formulation to deliver the enzyme into the deep lung alveoli of CF patients. The purihed glycoprotein contains 260 amino acids with an approximate molecular weight of 37,000 daltons [26], The primary amino-acid sequence is identical to that of the... 

Fuchs, H.J., D.S. Borowitz, D.H. Christiansen, E.M. Morris, M.L. Nash, B.W. Ramsey, B.J. Rosenstein, A.L. Smith, and M.E. Wohl, Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med, 1994. 331(10) 637 2. 

Aerosolized DNase (dornase) is a therapeutic protein designed for alveoli delivery to achieve local effects in the deep lung. Aerosolized DNase is formulated as a pulmonary dosage form, targeted for deep-lung delivery to reduce opportunistic infections due to the increased viscosity of mucus in the lung that affects respiratory function in patients with cystic fibrosis. 

Several portable inhalation devices have been developed and are being tested to determine whether they improve protein and peptide delivery via the airways. Aerosolized DNase has been shown in patients with cystic flbrosis to significantly reduce the buildup of mucus in the lung and the incidence of infections. Devices for delivery of therapeutic proteins to deep-lung alveoli to achieve systemic effects are also in development. These products are formulated so that the device aerosolizes the protein in a defined particle size range that cannot be easily achieved by means of conventional metered dose inhalers. 

Pot inhalation treatment of respiratory diseases a pharmaceutical DNase I aerosol Is on the market Pulmozyme is a sterile solution for respiratory use at a concentration of 1000 Genentech UnitafaiL [22]. It contains 1 mg/mL rhDNasc, sodium chloride as a tonicity modifier, calcium chloride as a stabilizer, and water for injection. Since deamidation is mnid at hirit nH and anaenation ncoin at low... 

O Donnell AE, Barker AF, Uowite JS, Fick RB. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group. Chest 1998 113(5) 1329-34. 

Fuchs HJ, Borwitz DS, Christainsen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med 1994 331 637-642. 

For inhalation treatment of respiratory diseases, a pharmaceutical DNase I aerosol is on the market. Pulmozyme is a sterile solution for respiratory use at a concentration of 1000 Genentech Units/mL [22]. It contains 1 mg/mL rhDNase, sodium chloride as a tonicity modifier, calcium chloride as a stabilizer, and water for injection. Since deamidation is rapid at high pH and aggregation occurs at low pH, a nearly neutral solution (pH 6.3) is required. It is administered by means of a compressed air-driven nebulizer. Each 2.5-mL single-unit ampule will deliver 2.5 mg of rhDNase to the nebulizer chamber. The efficacy of DNase inhalation therapy largely depends on the aerosol quality and characteristics, which determine the respirable fraction. Significant differences were found between the different aerosol drug-delivery systems [68,81]. 

Recombinant human deoxyribonnclease I. Delivered by aerosol mist. The protein is produced by genetically engineered CHO cells containing DNA encoding for the native human protein, DNase I. 260aa. 

The only U.S. FDA-approved DNase product, Dornase alpha (inhalation solution), has been developed as a therapeutic agent for the management of CF. The product is supplied in single-use ampules delivering 2.5 ml of a sterile, clear, colorless solution containing 1.0 mg/ml of dornase alpha with no preservative. Administration is by nebulizer aerosol delivery systems. 

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