Cystic fibrosis pulmonary system

These drugs have also been studied for possible use in other conditions. Clinical studies show distinct benefit in some patients with pulmonary arterial hypertension, and possible benefit in systemic hypertension, cystic fibrosis, and benign prostatic hyperplasia. Preclinical studies suggest that sildenafil may be useful in preventing apoptosis and cardiac remodeling after ischemia and reperfusion. 

Although routine oral delivery of proteins has not been realized, some protein formulations have been developed for pulmonary delivery. Pulmonary delivery can result in either parenteral or local administration of the drug and, like oral delivery, is considered non-invasive. As with other routes of delivery, the size of the protein may limit its ability to be delivered systemi-cally via the pulmonary route of administration. Pulmozyme , a DNase-based formulation approved for the treatment of cystic fibrosis (CF), is delivered to the lungs by a nebulizer to clear blockage of the airways in the CF patient.Formulations for insulin to be administered by inhalation for systemic delivery of... 

Cystic fibrosis is a heterogeneous, autosomal recessive genetic disease associated with abnormal exocrine gland function, which affects multiple organs, including the gastrointestinal, pulmonary, and reproductive systems. Cystic fibrosis is... 

Airway administration of liposome complexes was used for the treatment of pulmonary diseases including cystic fibrosis. Cationic liposome/DNA complex showed no adverse effect towards airway epithelial integrity (190) therefore, the cationic lipid-based delivery system proved to be appropriate for use in human trials for cystic fibrosis (CF). A series of pre-clinical trials were done in CF patients with intranasal instillation to evaluate the risk factors associated with the treatment (191-193). Because there was no apparent toxicity associated with lipoplexes as was seen from these trials, progress had been made in delivering the complexes to the entire lung by aerosol in CF patients (192,194,195). By nebulization, the DNA-liposome complex was delivered into the airways of mutant mice to obtain human cystic fibrosis transmem-... 

Although aerosols of various forms for treatment of respiratory disorders have been in use since the middle of the twentieth century, the interest in the use of pulmonary route for systemic drug delivery is recent. Interest in this approach has been further stimulated by the demonstration of potential utility of lung as a portal for entry of peptides and the feasibility of gene therapy for cystic fibrosis. It is important to understand the mechanism of macromolecule absorption by the lungs for an effective use of this route. 

Parenteral administration is the primary route of testing delivery for nucleic acid therapeutics irrespective of whether systemic or local effects are desired. However, to some extent, pulmonary and oral routes are also investigated as potential routes for local targeting to treat cystic fibrosis or colonic tissue (171-173). For nonparenteral delivery, the use of pharmaceutical excipients in the formulation is critical. In addition, the production costs of nucleic acid therapeutic-containing drug delivery systems should be minimized. Even for intravenously or subcutaneously injected nucleic acid-based therapeutics, the use of protective carriers is most likely necessary, and advantageous as compared to injection of the naked RNA or DNA. Carriers can be divided into viral or... 

Cystic fibrosis (CF) is a disorder of chloride ion transport in epithelial cells. It especially affects the cells that line the pulmonary and gastrointestinal systems, although the functions of other exocrine glands are also altered. 

Cystic fibrosis (CF) is the most common lethal genetic disease in the Caucasian population. The disease mainly involves the exocrine glands and thus affects a number of organ systems (Table 30-1). The more common manifestations of this disease involve the gastrointestinal and pulmonary systems, with premature mortality associated with the latter. Most of the pathology results from a defect in electrolyte transport caused by a loss of functional chloride channels in epithelial cells. The protean nature of this disease dictates that care be multidisciplinary with a wide variety of therapeutic interventions. 

There is epidemiologic evidence to suggest an increased prevalence of duodenal ulcers in patients with certain chronic diseases, but the pathophysiologic mechanisms of these associations are uncertain. A strong association exists in patients with systemic mastocytosis, multiple endocrine neoplasia type 1, chronic pulmonary diseases, chronic renal failure, kidney stones, hepatic cirrhosis, and ai-antitrypsin deficiency. An association may exist in patients with cystic fibrosis, chronic pancreatitis, Crohn s disease, coronary artery disease, polycythemia vera, and hyperparathyroidism. 

Pulmonary administration of medicines currently has the primary objective to achieve local effects in the respiratory tract of patients with chronic diseases like asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). For half a century, inhalation therapy has been the cornerstone in the management of these diseases and the often life-time therapies aim to suppress inflammatory processes and bacterial infection in order to reduce hospitalisations and to improve the patient s quality of life. They also give relief to the patient in moments of bronchoconstriction. The advantages of pulmonary administration of medicines for local treatment are well known. The active substances are delivered directly to the site of action which leads to a faster response than via the systemic route. It may also result in higher local active substance concentrations and this could reduce the total dose by as much as a factor 10 compared to oral or intravenous administration. This has the advantage that systemic side effects are reduced and in combination with being a non-invasive method of administration, inhalation therapy may lead to better patient compliance. 

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