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 a pulmonary infection due to a bacterial infective agent in a patient in need thereof, comprising,
aerosolizing a pharmaceutical formulation comprising a mixture of free fluoroquinolone antibiotic agent, an aqueous dispersion of fluoroquinolone antibiotic agent encapsulated in a plurality of liposomes having a mean diameter from about 0.01 microns to about 3.0 microns, and a pharmaceutical excipient, via a nebulizer, to form an aerosolized pharmaceutical formulation, wherein the lipid component of the plurality of liposomes consists of a phosphatidylcholine and cholesterol, and wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free fluoroquinolone antibiotic agent to the encapsulated fluoroquinolone antibiotic agent in the pharmaceutical formulation is between about 1:10 and about 10:1, and
administering the aerosolized pharmaceutical formulation to the lungs of the patient, wherein the aerosolized pharmaceutical formulation comprises free fluoroquinolone antibiotic agent in an amount effective to provide immediate bactericidal activity and liposomal encapsulated fluoroquinolone antibiotic agent in an amount effective to provide sustained bactericidal activity against.
2. The method of claim 1 , wherein the free fluoroquinolone antibiotic agent is free ciprofloxacin and the fluoroquinolone antibiotic agent encapsulated in the plurality of liposomes is ciprofloxacin.
3. The method of claim 1 , wherein the phosphatidylcholine is hydrogenated soy phosphatidylcholine (HSPC).
4. The method of claim 2 , wherein the phosphatidylcholine is hydrogenated soy phosphatidylcholine (HSPC).
5. The method of claim 1 , wherein the patient is a bronchiectasis patient.
6. The method of claim 2 , wherein the patient is a bronchiectasis patient.
7. The method of claim 3 , wherein the patient is a bronchiectasis patient.
8. The method of claim 4 , wherein the patient is a bronchiectasis patient.
9. The method of claim 1 , wherein the bacterial infective agent is Pseudomonas aeruginosa.
10. The method of claim 2 , wherein the bacterial infective agent is Pseudomonas aeruginosa.
11. The method of claim 3 , wherein the bacterial infective agent is Pseudomonas aeruginosa.
12. The method of claim 4 , wherein the bacterial infective agent is Pseudomonas aeruginosa.
13. The method of claim 5 , wherein the bacterial infective agent is Pseudomonas aeruginosa.
14. The method of claim 6 , wherein the bacterial infective agent is Pseudomonas aeruginosa.
15. The method of claim 7 , wherein the bacterial infective agent is Pseudomonas aeruginosa.
16. The method of claim 8 , wherein the bacterial infective agent is Pseudomonas aeruginosa.
17. The method of claim 1 , wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free fluoroquinolone antibiotic agent to the encapsulated fluoroquinolone antibiotic agent in the pharmaceutical formulation is between about 1:2 and about 2:1.
18. The method of claim 2 , wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free ciprofloxacin to the encapsulated ciprofloxacin in the pharmaceutical formulation is between about 1:2 and about 2:1.
19. The method of claim 4 , wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free ciprofloxacin to the encapsulated ciprofloxacin in the pharmaceutical formulation is between about 1:2 and about 2:1.
20. The method of claim 5 , wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free fluoroquinolone antibiotic agent to the encapsulated fluoroquinolone antibiotic agent in the pharmaceutical formulation is between about 1:2 and about 2:1.
21. The method of claim 6 , wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free ciprofloxacin to the encapsulated ciprofloxacin in the pharmaceutical formulation is between about 1:2 and about 2:1.
22. The method of claim 8 , wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free ciprofloxacin to the encapsulated ciprofloxacin in the pharmaceutical formulation is between about 1:2 and about 2:1.
23. The method of claim 13 , wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free fluoroquinolone antibiotic agent to the encapsulated fluoroquinolone antibiotic agent in the pharmaceutical formulation is between about 1:2 and about 2:1.
24. The method of claim 14 , wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free ciprofloxacin to the encapsulated ciprofloxacin in the pharmaceutical formulation is between about 1:2 and about 2:1.
25. The method of claim 16 , wherein prior to aerosolizing the pharmaceutical formulation, the ratio by weight of free ciprofloxacin to the encapsulated ciprofloxacin in the pharmaceutical formulation is between about 1:2 and about 2:1.
26. The method of claim 4 , wherein the pharmaceutical excipient comprises sucrose.
27. The method of claim 12 , wherein the pharmaceutical excipient comprises sucrose.
28. The method of claim 25 , wherein the pharmaceutical excipient comprises sucrose.
29. The method of claim 12 , wherein the nebulizer is a jet nebulizer.
30. The method of claim 25 , wherein the nebulizer is a jet nebulizer.