Sterically stabilized carrier for aerosol therapeutics, compositions and methods for treating the respiratory tract of a mammal

Abstract

The application disclosure provides a sterically stabilized liposome carrier encapsulating a selected drug for the aerosol delivery of the drug effectual in the treatment of a mammal, a composition containing the sterically stabilized liposome carrier and the selected drug effective for the treatment of airway hypersensitivity and inflammation such as of the lungs of a mammal as an aerosol, and a method of treatment using the composition. The composition disclosed herein provides effective treatment for the longer of a period of time at least twice as long as the selected drug alone or up to at least one week.

1 - 25 . (canceled) 
     
     
         26 . A sterically stabilized liposome carrier for use in treating diseases of the respiratory tract, wherein the sterically stabilized liposome carrier: (i) comprises a phosphatidylcholine (PC), a phosphatidylglycerol (PG), and a poly (ethylene glycol) distearoylphosphatidyl ethanolamine (PEG-DSPE); (ii) has a gel-liquid transition temperature from about −20° C. to about 44° C.; and (iii) is effective to reduce lung inflammation and/or airway hyperactivity upon inhalation of the sterically stabilized liposome carrier by a subject. 
     
     
         27 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier is effective to deposit the selected drug in the airways down to the alveoli and the alveolar tight junction. 
     
     
         28 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier has a gel-liquid transition temperature from about −10° C. to about 42° C. 
     
     
         29 . The sterically stabilized liposome carrier of  claim 26 , wherein the PC comprises synthetic palmitoyloleoyl-PG (POPC) and/or the PG comprises synthetic palmitoyloleoyl-PG (POPG). 
     
     
         30 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier is free of cholesterol. 
     
     
         31 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier further comprises cholesterol. 
     
     
         32 . The sterically stabilized liposome carrier of  claim 26 , wherein, upon inhalation of the sterically stabilized liposome carrier, the sterically stabilized liposome carrier binds to Type 2 pneumocytes in the lungs. 
     
     
         33 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier exhibits increased stability in plasma relative to a conventional liposome. 
     
     
         34 . The sterically stabilized liposome of  claim 26 , wherein the sterically stabilized liposome does not encapsulate a drug. 
     
     
         35 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier encapsulates a drug. 
     
     
         36 . The sterically stabilized liposome carrier of  claim 35 , wherein, upon inhalation of the sterically stabilized liposome carrier, the sterically stabilized liposome carrier and encapsulated drug are delivered to the alveoli and the alveolar tight junctions. 
     
     
         37 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier is not destroyed in the lungs upon inhalation of the sterically stabilized liposome carrier by the subject. 
     
     
         38 . The sterically stabilized liposome carrier of  claim 35 , wherein the drug comprises a corticosteroid drug, chromolyn sodium, albuterol sulfate, terbutaline, albuterol, ipratropium, pirbuterol, epinephrine, salmeterol, levalbuterol, formoterol, leukotriene inhibitor, antihistamines, anti-tuberculosis drugs, serine lung protease inhibitor, monophosphoryl lipid A, azelastine, theophylline, peptides for allergy immunology, amikacin, gentamicin, tobramycin, rifapentine, rifabutin, sparfloxacin, ciprofloxacin, quinolones, azithromycin, erythromycin, isoniazid, budesonide, flunisolide, triamcinolone, beclomethasone, fluticasone, mometasone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, cortisone, or betamethasone. 
     
     
         39 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier provides long stability to the alveoli and the respiratory upon inhalation of the sterically stabilized liposome carrier by the subject. 
     
     
         40 . The sterically stabilized liposome carrier of  claim 35 , wherein the sterically stabilized liposome carrier is effective to extend the effective life of the drug. 
     
     
         41 . The sterically stabilized liposome carrier of  claim 35 , wherein the drug is effective for treatment of the respiratory tract of a mammal. 
     
     
         42 . The sterically stabilized liposome carrier of  claim 35 , wherein the encapsulated drug has an greater effective life than an unencapsulated drug when administered in equivalent dosages. 
     
     
         43 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier contains from about 0.1 to about 99.4 mole percent phosphatidylcholine, from about 0.1 to about 99.4 phosphatidylglycerol and from about 0.5 to about 10 mole percent poly(ethylene glycol). 
     
     
         44 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier contains from about 60 to about 90 mole percent phosphatidylcholine, from about 10 to about 40 mole percent phosphatidylglycerol and from about 1 to about 5 mole percent poly(ethylene glycol). 
     
     
         45 . The sterically stabilized liposome carrier of  claim 26 , wherein the sterically stabilized liposome carrier contains from about 70 to about 80 mole percent phosphatidylcholine, from about 20 to about 30 mole percent phosphatidylglycerol, from about 2 to about 5 mole percent poly(ethylene glycol) and from about 1 to about 33 mole percent