Lipid-based compositions of antiinfectives for treating pulmonary infections and methods of use thereof
View Patent ↗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. A method for treating or providing prophylaxis against a pulmonary infection in a cystic fibrosis patient in need thereof, comprising, administering to the lungs of the cystic fibrosis 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 liposomes comprise a phosphatidylcholine and a sterol, and the aerosolized pharmaceutical composition comprises droplets of an aqueous solution or suspension.
2. The method of claim 1 , wherein the aminoglycoside is amikacin.
3. The method of claim 1 , wherein the aminoglycoside is gentamicin, kanamycin, neomycin, netilmicin, streptomycin, tobramycin or paromomycin.
4. The method of claim 1 , wherein the sterol is cholesterol.
5. The method of claim 2 , wherein the sterol is cholesterol.
6. The method of claim 1 , wherein the pulmonary infection is Pseudomonas aeruginosa.
7. The method of claim 1 , wherein the pulmonary infection is a mycobacterial infection.
8. The method of claim 1 , wherein the pulmonary infection is a Burkholderia infection.
9. The method of claim 7 , wherein the mycobacterial infection is Mycobacterium leprae, Mycobacterium africanum, Mycobacterium asiaticum, Mycobacterium avium - intracellulaire, Mycobacterium chelonae, Mycobacterium abscessus, Mycobacterium chelonae abscessus, Mycobacterium fallax, Mycobacterium fortuitum, Mycobacterium kansasii, Mycobacterium leprae, Mycobacterium malmoense, Mycobacterium shimoidei, Mycobacterium simiae, Mycobacterium szulgai, Mycobacterium xenopi or Mycobacterium tuberculosis.
10. The method of claim 9 , wherein the mycobacterial infection is Mycobacterium abscessus or Mycobacterium avium - intracellulaire.
11. The method of claim 1 , wherein the liposomal encapsulated aminoglycoside comprises a mixture of unilamellar vesicles and multilamellar vesicles.
12. The method of claim 1 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).
13. The method of claim 2 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).
14. The method of claim 1 , wherein a ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:100 and about 100:1.
15. The method of claim 1 , wherein a ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:10 and about 10:1.
16. The method of claim 1 , wherein a ratio by weight of free aminoglycoside to the aminoglycoside encapsulated in the liposome is between about 1:2 and about 2:1.
17. The method of claim 2 , wherein the liposomal encapsulated amikacin comprises unilamellar and multilamellar vesicles.
18. The method of claim 1 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol.
19. The method of claim 2 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol.
20. The method of claim 6 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol.
21. The method of claim 7 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol.
22. The method of claim 2 , wherein a ratio by weight of free amikacin to the amikacin encapsulated in the liposome is between about 1:100 and about 100:1.
23. The method of claim 2 , wherein a ratio by weight of free amikacin to the amikacin encapsulated in the liposome is between about 1:10 and about 10:1.
24. The method of claim 2 , wherein a ratio by weight of free amikacin to the amikacin encapsulated in the liposome is between about 1:2 and about 2:1.
25. The method of claim 1 , wherein the pulmonary infection is bronchiectasis.
26. The method of claim 2 , wherein the pulmonary infection is bronchiectasis.
27. The method of claim 2 , wherein the pulmonary infection is Pseudomonas aeruginosa.
28. The method of claim 25 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).
29. The method of claim 25 , wherein the sterol is cholesterol.
30. The method of claim 25 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol.
31. The method of claim 26 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).
32. The method of claim 26 , wherein the sterol is cholesterol.
33. The method of claim 26 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol.
34. The method of claim 27 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC).
35. The method of claim 27 , wherein the sterol is cholesterol.
36. The method of claim 27 , wherein the phosphatidylcholine is dipalmitoylphosphatidylcholine (DPPC) and the sterol is cholesterol.
37. The method of claim 1 , wherein the pharmaceutical formulation is administered to the lungs of the cystic fibrosis patient via an electronically operated nebulizer.
38. The method of claim 2 , wherein the pharmaceutical formulation is administered to the lungs of the cystic fibrosis patient via an electronically operated nebulizer.
39. The method of claim 6 , wherein the pharmaceutical formulation is administered to the lungs of the cystic fibrosis patient via an electronically operated nebulizer.
40. The method of claim 26 , wherein the pharmaceutical formulation is administered to the lungs of the cystic fibrosis patient via an electronically operated nebulizer.
41. The method of claim 27 , wherein the pharmaceutical formulation is administered to the lungs of the cystic fibrosis patient via an electronically operated nebulizer.
42. The method of claim 1 , wherein the mean diameter of the liposomes in the formulation is 0.01 μm to 3.0 μm.
43. The method of claim 2 , wherein the mean diameter of the liposomes in the formulation is 0.01 μm to 3.0 μm.
44. The method of claim 6 , wherein the mean diameter of the liposomes in the formulation is 0.01 μm to 3.0 μm.
45. The method of claim 25 , wherein the mean diameter of the liposomes in the formulation is 0.01 μm to 3.0 μm.
46. The method of claim 27 , wherein the mean diameter of the liposomes in the formulation is 0.01 μm to 3.0 μm.
47. The method of claim 42 , wherein the mean diameter of the liposomes in the formulation is 0.2 μm to 1.0 μm.
48. The method of claim 43 , wherein the mean diameter of the liposomes in the formulation is 0.2 μm to 1.0 μm.
49. The method of claim 44 , wherein the mean diameter of the liposomes in the formulation is 0.2 μm to 1.0 μm.
50. The method of claim 45 , wherein the mean diameter of the liposomes in the formulation is 0.2 μm to 1.0 μm.
51. The method of claim 46 , wherein the mean diameter of the liposomes in the formulation is 0.2 μm to 1.0 μm.