Delivery of Submicrometer and Nanometer Aerosols to the Lungs using Hygroscopic Excipients or Dual Stream Nasal Delivery

Abstract

Pharmaceutically engineered aerosols (e.g. submicrometer and nano-particles and droplets) containing a hygroscopic growth excipient or agent are employed to improve the delivery of respiratory aerosols to the lung. Inclusion of the hygroscopic agent results in near zero depositional loss in the nose-mouth-throat regions and near 100% deposition of the aerosol in the lung. Targeting of the aerosol to specific lung depths is also possible. In addition, methods and apparatuses for delivering aerosols to the lung are provided. The aerosol is delivered to one nostril of a patient while a relatively high humidity gaseous carrier is delivered to the other nostril, resulting in post-nasopharyngeal growth of the aerosol to a size that promotes deposition in the lung.

1 - 48 . (canceled) 
     
     
         49 . A method of delivering aerosolized particles or droplets to a region of a respiratory system in a patient, said method comprising:
 generating particles or droplets comprising a therapeutic agent and a hygroscopic excipient;   delivering the particles or droplets to a first region of the respiratory system, wherein the particles or droplets have an initial diameter to permit substantially unimpeded travel of the particles or the droplets through the first region of the respiratory system without significant deposition;   exposing the particles or the droplets to relative humidity in the respiratory system thereby increasing diameter of the particles or the droplets to a size that generally is not exhaled; and   depositing the particles or droplets in a portion of a nasal cavity due to the increased diameter of the particle or the droplets.   
     
     
         50 . The method of  claim 49 , wherein the hygroscopic agent comprises a salt, a sugar, an acid, a glycol, or a lactam. 
     
     
         51 . The method of  claim 49 , wherein the therapeutic agent is selected from the group consisting of agents for the treatment of respiratory disorders, anesthesia agents, nucleic acid molecules, anti-pain agents, anti-inflammation agents, anti-depressants and other mood altering drugs, anti-viral agents, anti-bacterial agents, anti-fungal agents, anti-cancer agents, hormones, benzodiazepines and calcitonin. 
     
     
         52 . The method of  claim 49 , wherein the relative humidity is a natural humidity in the respiratory system. 
     
     
         53 . The method of  claim 49 , wherein the ratio of the increased diameter to the initial diameter is greater than about 1 and less than about 5. 
     
     
         54 . The method of  claim 49 , wherein the ratio of the increased diameter to the initial diameter is from about 3 to about 5. 
     
     
         55 . The method of  claim 49 , wherein the increased diameter of the particles or droplets is in the range from about 1 μm to about 10 μm. 
     
     
         56 . The method of  claim 49 , wherein the increased diameter of the particles or droplets is 4 urn or above. 
     
     
         57 . The method of  claim 49 , wherein depositing the particles comprise depositing particles having a first initial diameter and a second initial diameter, wherein the second initial diameter is greater than the first initial diameter, and wherein deposition of the first initial diameter particles in the nasal cavity is less than deposition of the second initial diameter particles in the nasal cavity. 
     
     
         58 . The method of  claim 49 , wherein generating particles or droplets comprises generating the particles or droplets with a condensational aerosol generator, a metered dose inhaler, a nebulizer, dry powder inhaler, or a soft mist inhaler. 
     
     
         59 . A device for delivering aerosolized particles or droplets to a region of a respiratory system in a patient, said device comprising:
 an aerosol generator;   a therapeutic agent and a hygroscopic excipient contained in the aerosol generator, wherein the aerosol generator generates particles or droplets containing the therapeutic agent and the hygroscopic excipient,   wherein the particles or droplets have an initial diameter to permit substantially unimpeded travel of the particles or the droplets through the first region of the respiratory system without significant deposition, and   wherein exposure of the particles or droplets to relative humidity in the respiratory system increases diameter of the particles or droplets to a size that generally is not exhaled, and   wherein the increased diameter of the particles or droplets results in deposition of the particles or droplets in a portion of a nasal cavity.   
     
     
         60 . The device of  claim 59 , wherein the therapeutic agent is selected from the group consisting of agents for the treatment of respiratory disorders, anesthesia agents, nucleic acid molecules, anti-pain agents, anti-inflammation agents, anti-depressants and other mood altering drugs, anti-viral agents, anti-bacterial agents, anti-fungal agents, anti-cancer agents, hormones, benzodiazepines and calcitonin. 
     
     
         61 . The device of  claim 59 , wherein the hygroscopic agent comprises a salt, a sugar, an acid, a glycol, or a lactam. 
     
     
         62 . The device of  claim 59 , wherein the ratio of the increased diameter to the initial diameter is greater than about 1 and less than about 5. 
     
     
         63 . The device of  claim 59 , wherein the ratio of the increased diameter to the initial diameter is from about 3 to about 5. 
     
     
         64 . The device of  claim 59 , wherein the increased diameter of the particles or droplets is in the range from about 1 μm to about 10 μm. 
     
     
         65 . The device of  claim 59 , wherein the increased diameter of the particles or droplets is 4 μm or above. 
     
     
         66 . The device of  claim 59 , wherein the aerosol generator comprises a condensational aerosol generator, a metered dose inhaler, a nebulizer, dry powder inhaler, or a soft mist inhaler. 
     
     
         67 . A device for delivering aerosolized particles or droplets to a region of a respiratory system in a patient, said device comprising:
 a metered dose inhaler;   a therapeutic agent and a hygroscopic excipient contained in the metered dose inhaler, wherein the metered dose inhaler generates particles or droplets containing the therapeutic agent and the hygroscopic excipient,   wherein the particles or droplets have an initial diameter to permit substantially unimpeded travel of the particles or the droplets through the first region of the respiratory system without significant deposition, and   wherein exposure of the particles or droplets to relative humidity in the respiratory system increases diameter of the particles or droplets to a size that generally is not exhaled, and   wherein the increased diameter of the particles or droplets results in deposition of the particles or droplets in a portion of a nasal cavity.   
     
     
         68 . The device of  claim 67 , wherein the therapeutic agent is selected from the group consisting of agents for the treatment of respiratory disorders, anesthesia agents, nucleic acid molecules, anti-pain agents, anti-inflammation agents, anti-depressants and other mood altering drugs, anti-viral agents, anti-bacterial agents, anti-fungal agents, anti-cancer agents, hormones, benzodiazepines and calcitonin. 
     
     
         69 . The device of  claim 67 , wherein the hygroscopic agent comprises a salt, a sugar, an acid, a glycol, or a lactam. 
     
     
         70 . The device of  claim 67 , wherein the ratio of the increased diameter to the initial diameter is greater than about 1 and less than about 5. 
     
     
         71 . The device of  claim 67 , wherein the ratio of the increased diameter to the initial diameter is from about 3 to about 5. 
     
     
         72 . The device of  claim 67 , wherein the increased diameter of the particles or droplets is in the range from about 1 μm to about 10 μm. 
     
     
         73 . The device of  claim 67 , wherein the increased diameter of the particles or droplets is 4 μm or above. 
     
     
         74 . Use of a therapeutic agent and an excipient for treating respiratory diseases, wherein the therapeutic agent and the excipient are delivered from an aerosol generator to form particles or droplets delivered in an aerosol to targeted tissue along a respiratory tract in a patient, the particles having an initial diameter to minimize deposition of the particles in a first portion of the respiratory tract away from the targeted tissue, wherein the targeted tissue comprises the nasal tissue, and
 wherein the particles or droplets increase in diameter when exposed to relative humidity in the respiratory tract, and   wherein the increased diameter of the particle or droplets enhances deposition of the particles in the targeted tissue.   
     
     
         75 . The use of the therapeutic agent and the excipient as in  claim 74 , wherein the therapeutic agent is selected from the group consisting of agents for the treatment of respiratory disorders, anesthesia agents, nucleic acid molecules, anti-pain agents, anti-inflammation agents, anti-depressants and other mood altering drugs, anti-viral agents, anti-bacterial agents, anti-fungal agents, anti-cancer agents, hormones, benzodiazepines and calcitonin. 
     
     
         76 . The use of the therapeutic agent and the excipient as in  claim 74 , wherein the targeted tissue comprises tissue in a nasal cavity. 
     
     
         77 . The use of the therapeutic agent and the excipient as in  claim 74 , wherein the ratio of the increased diameter to the initial diameter is greater than about 1 and less than about 5. 
     
     
         78 . The use of the therapeutic agent and the excipient as in  claim 74  wherein the ratio of the increased diameter to the initial diameter is from about 3 to about 5. 
     
     
         79 . The use of the therapeutic agent and the excipient as in  claim 74 , wherein the increased diameter of the particles or droplets is in the range from about 1 μm to about 10 μm. 
     
     
         80 . The use of the therapeutic agent and the excipient as in  claim 74 , wherein the increased diameter of the particles or droplets is 4 μm or above. 
     
     
         81 . The use of the therapeutic agent and the excipient as in  claim 74 , wherein the aerosol generator comprises a condensational aerosol generator, a metered dose inhaler, a nebulizer, dry powder inhaler, or a soft mist inhaler. 
     
     
         82 . Use of a steroid and a salt for treating nasal tissue, wherein the steroid and the salt are delivered from a metered dose inhaler to form particles or droplets delivered in an aerosol to targeted nasal tissue along a respiratory tract in a patient, the particles having an initial diameter to minimize deposition of the particles in a first portion of the respiratory tract away from the targeted tissue, wherein the targeted tissue comprises the nasal tissue, and
 wherein the particles or droplets increase in diameter when exposed to relative humidity in the respiratory tract, and   wherein the increased diameter of the particle or droplets enhances deposition of the particles in the targeted tissue.   
     
     
         83 . The use of the steroid and the salt as in  claim 82 , wherein the steroid is selected from the group consisting of agents for the treatment of respiratory disorders. 
     
     
         84 . The use of the steroid and the salt as in  claim 82 , wherein the ratio of the increased diameter to the initial diameter is greater than about 1 and less than about 5. 
     
     
         85 . The use of the steroid and the salt as in  claim 82 , wherein the ratio of the increased diameter to the initial diameter is from about 3 to about 5. 
     
     
         86 . The use of the steroid and the salt as in  claim 82  wherein the increased diameter of the particles or droplets is in the range from about 1 μm to about 10 μm. 
     
     
         87 . The use of the steroid and the salt as in  claim 82 , wherein the increased diameter of the particles or droplets is 4 μm or above.