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Protein delivery by aerosol

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. [Pg.54]

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. [Pg.369]

In the aerosol solvent extraction system (ASES), the protein is dissolved in a compatible solvent (i.e., water or DMSO) and then introduced by atomization into supercritical CO2 (12,13). The solvent is extracted from the droplet, and the protein precipitates to form particles with appropriate sizes for pulmonary delivery (see Note 3). CO2 is then removed by venting off and the particles are collected. Insulin powders (see Note 4) made by this method possess a mean geometric diameter of 9.6 xm, and 22% of the powder was in the respirable range (0.5-6 p,m) (12). [Pg.171]

Dumont JA, Bitonti AJ, Clark D, Evans S, Pickford M, Newman SP. Delivery of an erythropoietin-Fc fusion protein by inhalation in humans through an immunoglobulin transport pathway. I Aerosol Med 2005 18(3) 294-303. [Pg.274]

Akwete, A.L., Gupta, P.K., Eds. Niven, delivery of biotherapeutics by inhalation aerosol. In Inhalation Delivery of Therapeutic Peptides and Proteins, Marcel Dekker, Inc. New York, 1997 151-231. [Pg.1285]


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