Deoxyribonuclease inhalation

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. 

Dosage form Pulmozyme Inhalation Solution is a sterile, preservative-free, highly purihed solution of recombinant human deoxyribonuclease I (dornase alfa). Each Pulmozyme single-use ampule will deliver 2.5 ml of the solution to the nebulizer bowl. The aqueous solution contains domase alfa l.Omg/ml. 

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. 

L Gonda. Inhalation therapy with recombinant human deoxyribonuclease I. Adi. Drug Dciiv. Rev. 19 37-46 (1996). 

Dornase alfa is phosphorylated glycosylated recombinant human deoxyribonuclease. It is given daily by inhalation of a nebulised solution containing 2500 units (2.5 mg). It is of modest value only in patients with cystic fibrosis, whose genetic defect in chloride transport causes particularly viscous sputum. The blocked airways, as well as the sputum itself, are a trap for pathogens and the lysis of invading neutrophils leads to substantial levels of free and very viscous DNA within the CF airways. 

Protein and peptide therapeutics currently represent eight of the top 100 prescription pharmaceuticals in the U.S., and biotechnology products are projected to account for 15% of the total US. prescription drug market by 2003. Of the protein and peptide products now on the market, many are administered as daily injections, though several are delivered by noninvasive routes. For example, desmopressin is delivered as a nasal spray, and deoxyribonuclease I is administered by inhalation. Although cyclosporin A is orally active, as yet there are no general means to confer oral bioavailability to peptides and proteins. A major advance in delivery of peptides was achieved with the introduction of a monthly injectable, biodegradable microsphere formulation of LHRH. 

---