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theses

Idiopathic Pulmonary Fibrosis (IPF) is very insidious and untreatable disease. While many investigations are focused on the pathogenesis of the disease this disorder does not have reliable therapeutic options and an effective therapy has yet to be identified and developed. Pulmonary fibrosis has been mainly treated for secondary symptoms with some success, but unfortunately patients succumb to the disease. While cystic fibrosis is caused by mutation in chlorine transporter gene CFTR, idiopathic pulmonary fibrosis is developed similarly to cancer due to various environmental factors combined with genetic. Antibiotic treatments have prolonged the survival rate of children suffering from cystic fibrosis to forty years. Meanwhile, various treatments for idiopathic pulmonary fibrosis were less successful with general survival rate less than 3 years. All of the current treatments address secondary symptoms rather than the cause of the disease. Therefore, it is very vital to develop new treatment for debilitating fibrotic diseases. In our study we focused on the pulmonary form of fibrosis. It is natural to use local administration of drugs by inhalation for treating of - respiratory diseases. Some of the respiratory drugs nowadays are being repositioned for local treatment. With successful inhalation devices and monitoring, local delivery to the lungs has higher efficacy due to administering lower doses directly at the site of action and potentially eliminating systemic toxicity. Nanotechnology is referred to the field that deals with particles in nanometer size range, which gives higher surface area and bioavailability to its desired therapeutic components. Nanoparticles improve treatments by increasing stability, solubility, and providing sustained release of therapeutic agent, which results in reduced dosage frequency and higher patient compliance. The overall purpose of this work is to develop, characterize and evaluate in vitro and in vivo novel inhalational nanotechnology-based treatment for idiopathic pulmonary - and cystic fibroses. In the dissertation we are planning to focus on the: (1) to design bleomycin animal model of idiopathic pulmonary fibrosis and to test novel inhalational treatment approach using liposomal form of Prostaglandin E2 (PGE2); (2) to develop multifunctional targeted nanosystem for the delivery of siRNA and PGE2 into the lungs of mice with IPF; (3) to develop and evaluate nanosystem containing two drugs with different mechanisms of action for treatment of cystic fibrosis.

ETD_6730

Ph.D.

Includes bibliographical references

by Vera Ivanova

doi:10.7282/T3PN97M7

ETD doctoral

The author owns the copyright to this work.