Lipid-based compositions of antiinfectives for treating pulmonary infections and methods of use thereof

Abstract

A system for treating or providing prophylaxus against a pulmonary infection is disclosed comprising: a) a pharmaceutical formulation comprising a mixture of free antiinfective and antiinfective encapsulated in a lipid-based composition, and b) an inhalation delivery device. A method for providing prophylaxis against a pulmonary infection in a patient and a method of reducing the loss of antiinfective encapsulated in a lipid-based composition upon nebulization comprising administering an aerosolized pharmaceutical formulation comprising a mixture of free antiinfective and antiinfective encapsulated in a lipid-based composition is also disclosed.

1 .- 45 . (canceled) 
     
     
         46 . A method for treating or providing prophylaxis against a pulmonary infection in a patient in need thereof comprising, administering to the lungs of the patient an aerosolized pharmaceutical composition comprising free aminoglycoside in an amount effective to provide immediate bactericidal activity against the pulmonary infection and liposomal encapsulated aminoglycoside in an amount effective to provide sustained bactericidal activity against the pulmonary infection, wherein the lipid component of the liposome consists of electrically neutral lipids, wherein the electrically neutral lipids comprise a phosphatidylcholine and a sterol, and the aerosolized pharmaceutical composition comprises droplets of an aqueous solution or suspension. 
     
     
         47 . the method of  claim 46 , wherein the aminoglycoside is amikacin. 
     
     
         48 . The method of  claim 46 , wherein the aminoglycoside is gentamicin, kanamycin, neomycin, netilmicin, streptomycin, tobramycin or paromomycin. 
     
     
         49 . The method of  claim 46 , wherein the sterol is cholesterol. 
     
     
         50 . The method of  claim 46 , wherein the pulmonary infection is  Pseudomonas aeruginosa.    
     
     
         51 . The method of  claim 46  wherein the pulmonary infection is a mycobacterial infection. 
     
     
         52 . The method of  claim 46 , wherein the pulmonary infection is a  Burkholderia  infection. 
     
     
         53 . The method of  claim 51 , wherein the mycobacterial infection is  Mycobacterium leprae, Mycobacterium africamum, Mycobacterium asiaticum Mycobacterium avium - intracellulare, Mycobacterium chelonae, Mycobacterium abscessus, Mycobacterium chelonae - abscessus, Mycobacterium fallax, Mycobacterium fortuitum, Mycobacterium kansasil, Mycobacterium leprae, Mycobacterium malmoense, Mycobacterium shimoidei, Mycobacterium simiae, Mycobacterium szulgai, Mycobacterium xenopi  or  Mycobacterium tuberculosis.    
     
     
         54 . The method of  claim 53 , wherein the mycobacterial infection is  Mycobacterium abscessus  or  Mycobacterium avium intracellulare.    
     
     
         55 . The method of  claim 46 , wherein the liposomal encapsulated aminoglycoside comprises a mixture of unilamellar vesicles and multilamellar vesicles. 
     
     
         56 . The method of  claim 46 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC). 
     
     
         57 . The method of  claim 46 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol. 
     
     
         58 . The method of  claim 46 , wherein a ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:100 and about 100:1. 
     
     
         59 . The method of  claim 46 , wherein a ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:10 and about 10:1. 
     
     
         60 . The method of  claim 46 , wherein a ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:2 and about 2:1. 
     
     
         61 . The method of  claim 46 , wherein the liposomal encapsulated amikacin comprises unilamellar and multilamellar vesicles. 
     
     
         62 . The method of  claim 47 , wherein the sterol is cholesterol. 
     
     
         63 . The method of  claim 47 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC). 
     
     
         64 . The method of  claim 47 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol. 
     
     
         65 . The method of  claim 47 , wherein a ratio by weight of free amikacin to the amikacin encapsulated in the liposome is between about 1:100 and about 100:1. 
     
     
         66 . The method of  claim 47 , wherein a ratio by weight of free amikacin to the amikacin encapsulated in the liposome is between about 1:10 and about 10:1. 
     
     
         67 . The method of  claim 47 , wherein a ratio by weight of free amikacin to the amikacin encapsulated in the liposome is between about 1:2 and about 2:1.