Use of nanoparticles for treating respiratory infections associated with cystic fibrosis
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Publication Number
US-12115250-B2
Publication Date
2024-10-15
Expiration Date
Abstract
This disclosure relates to metal nanoparticle compositions and methods for treating respiratory infections associated with cystic fibrosis. An amount of nonionic, ground state metal nanoparticles are administered to a patient via inhalation. The metal nanoparticles have properties that enable effective transport through the viscous mucus layer to the epithelia and surrounding tissues, killing or deactivating infecting microbes at the targeted respiratory tissue and throughout the overlying mucus layer.
Core Innovation
The invention relates to treating a bacterial respiratory infection in a patient with cystic fibrosis and a thick viscous mucus layer in the lungs caused by cystic fibrosis. The method includes administering a treatment composition via inhalation such that the lungs contain a thick viscous mucus layer and the bacterial respiratory infection is caused by one or more selected bacteria. The bacteria are located in both the thick viscous mucus layer and infected respiratory tissue.
The treatment composition comprises nonionic, ground state, spherical silver nanoparticles that are uncoated and uncoordinated with no external edges or bond angles. The nanoparticles are non-crystalline and have a mean diameter in a range of about 1 nm to about 20 nm with a particle size distribution such that at least 99% of the silver nanoparticles have a diameter within 30% of the mean diameter. The composition is formulated for inhalation and is designed to treat the infection by penetrating the thick viscous mucus layer, reaching infected respiratory tissue, and killing the bacteria in both locations.
A central aspect is killing without the release of silver ions. The invention also encompasses specific carrier formulations for administration via inhalation, including a carrier comprising saline solution and at least one of a carbohydrate, amino acid, buffer, alcohol, or polyalcohol. The disclosed bacterial scope includes drug-resistant respiratory pathogens associated with cystic fibrosis, with provisos excluding methicillin-resistant Staphylococcus aureus and Pneumocystis.
Claims Coverage
The independent claims cover three inventive method formulations for treating cystic fibrosis-associated bacterial respiratory infections via inhalation of uncoated nonionic ground state spherical silver nanoparticles with controlled size distribution and no silver-ion release; two claims additionally specify a saline-based carrier with selected excipients, and one claim focuses on Burkholderia cepacia complex. The inventive features consistently require penetration of thick viscous mucus, reaching infected respiratory tissue, and killing bacteria in both locations without silver-ion release.
Inhaled uncoated nonionic ground state spherical silver nanoparticles for cystic fibrosis mucus penetration and bacterial killing without silver-ion release
A method for treating a bacterial respiratory infection in a patient with cystic fibrosis and a thick mucus layer in the patient's lungs caused by cystic fibrosis by administering via inhalation a treatment composition comprising nonionic, ground state, spherical silver nanoparticles having a mean diameter in a range of about 1 nm to about 20 nm and a particle size distribution such that at least 99% of the silver nanoparticles have a diameter within 30% of the mean diameter; the nanoparticles are non-crystalline with no external edges or bond angles and are uncoated; and a carrier formulated for administration via inhalation; wherein the treatment composition penetrates the thick viscous mucus layer, reaches the infected respiratory tissue, and kills the bacteria in both the thick viscous mucus layer and the infected respiratory tissue without the release of silver ions.
Saline plus selected excipients carrier with uncoated nonionic non-crystalline spherical silver nanoparticles that do not release silver ions
A method for treating a bacterial respiratory infection in a patient with cystic fibrosis and a thick mucus layer in the patient's lungs caused by cystic fibrosis by administering via inhalation a treatment composition comprising nonionic, ground state, non-crystalline spherical silver nanoparticles having no external edges or bond angles and that do not release silver ions; having a mean diameter in a range of about 1 nm to about 20 nm and a particle size distribution such that at least 99% of the silver nanoparticles have a diameter within 30% of the mean diameter; wherein the nanoparticles are uncoated; and a carrier formulated for administration via inhalation, wherein the carrier comprises a saline solution and at least one of a carbohydrate, amino acid, buffer, alcohol, or polyalcohol; wherein the treatment composition penetrates the thick viscous mucus layer, reaches the infected respiratory tissue, and kills the bacteria in both the thick viscous mucus layer and the infected respiratory tissue without the release of silver ions.
Burkholderia cepacia complex-specific cystic fibrosis treatment using inhaled nonionic ground state uncoated spherical silver nanoparticles without silver-ion release
A method for treating a bacterial respiratory infection caused by Burkholderia cepacia complex in a cystic fibrosis patient having a thick mucus layer in the patient's lungs caused by cystic fibrosis by administering a treatment composition via inhalation into the patient's lungs comprising nonionic, ground state, spherical silver nanoparticles having a mean diameter in a range of about 4 nm to about 12 nm and a particle size distribution such that at least 99% of the silver nanoparticles have a diameter within 30% of the mean diameter; wherein the nanoparticles are non-crystalline with no external edges or bond angles and are uncoated; and a carrier formulated for administration via inhalation; wherein the treatment composition penetrates the thick viscous mucus layer, reaches the infected respiratory tissue, and killing the Burkholderia cepacia complex in both the thick viscous mucus layer and the infected respiratory tissue without the release of silver ions.
The claims center on inhalation administration to cystic fibrosis patients with thick viscous mucus using nonionic ground state uncoated non-crystalline spherical silver nanoparticles with controlled size distribution, no external edges or bond angles, and an inhalable carrier; the nanoparticles penetrate thick viscous mucus, reach infected respiratory tissue, and kill bacteria in both locations without silver-ion release. Two claims further refine the carrier to include saline with selected excipients, and one claim narrows the method to Burkholderia cepacia complex.
Stated Advantages
Killing bacteria in both the thick viscous mucus layer and infected respiratory tissue.
Killing without the release of silver ions.
Penetrating the thick viscous mucus layer and reaching infected respiratory tissue.
Documented Applications
Treating cystic fibrosis-associated bacterial respiratory infections in lungs containing a thick viscous mucus layer via inhalation of a treatment composition comprising specified silver nanoparticles.
Treating bacterial respiratory infection caused by Burkholderia cepacia complex in a cystic fibrosis patient via inhalation of the specified silver nanoparticle treatment composition.
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