Lipid-based compositions of antiinfectives for treating pulmonary infections and methods of use thereof
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 patient in need thereof, comprising:
administering to the lungs of the patient via an inhalation delivery device, a pharmaceutical formulation comprising a mixture of free quinolone antibiotic agent, a quinolone antibiotic agent encapsulated in a plurality of liposomes, and a pharmaceutical excipient, wherein the formulation is a solution or a suspension, the ratio by weight of free quinolone antibiotic agent to the encapsulated quinolone antibiotic agent is between about 1:10 and about 10:1 and the lipid component of the plurality of liposomes consists of electrically neutral lipids,
wherein the pharmaceutical formulation is administered as an aerosolized pharmaceutical formulation, and the aerosolized pharmaceutical formulation comprises free quinolone antibiotic agent in an amount effective to provide immediate bactericidal activity against the pulmonary infection and liposomal encapsulated quinolone antibiotic agent in an amount effective to provide sustained bactericidal activity against the pulmonary infection.
2. The method of claim 1 , wherein the quinolone antibiotic agent is a fluoroquinolone.
3. The method of claim 1 , wherein the quinolone antibiotic agent is ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, oxolinic acid, gemifloxacin, or perfloxacin.
4. The method of claim 1 , wherein the quinolone antibiotic agent is ciprofloxacin.
5. The method of claim 1 , wherein the electrically neutral lipids consist of an electrically neutral phospholipid and a sterol.
6. The method of claim 1 , wherein the electrically neutral lipids consist of a phosphatidylcholine and a sterol.
7. The method of claim 6 , wherein the phosphatidylcholine is hydrogenated soy phosphatidylcholine (HSPC).
8. The method of claim 6 , wherein the sterol is cholesterol.
9. The method of claim 7 , wherein the sterol is cholesterol.
10. The method of claim 1 , wherein the electrically neutral lipids consist of hydrogenated soy phosphatidylcholine (HSPC) and cholesterol and the quinolone antibiotic agent is a fluoroquinolone.
11. The method of claim 1 , wherein the electrically neutral lipids consist of a phosphatidylcholine and a sterol, and the quinolone antibiotic agent is ciprofloxacin.
12. The method of claim 1 , wherein the electrically neutral lipids consist of a phosphatidylcholine and cholesterol, and the quinolone antibiotic agent is ciprofloxacin.
13. The method of claim 1 , wherein the electrically neutral lipids consist of hydrogenated soy phosphatidylcholine (HSPC) and cholesterol and the quinolone antibiotic agent is ciprofloxacin.
14. The method of claim 1 , wherein the mean diameter of the plurality of liposomes is 0.01 micron to 3.0 microns.
15. The method of claim 14 , wherein the mean diameter of the plurality of liposomes is 0.2 micron to 1.0 micron.
16. The method of claim 1 , wherein the ratio by weight of free quinolone antibiotic agent to the encapsulated quinolone antibiotic agent is between about 1:2 and about 2:1.
17. The method of claim 13 , wherein the ratio by weight of free ciprofloxacin to the encapsulated ciprofloxacin is between about 1:2 and about 2:1.
18. The method of claim 1 , wherein the pulmonary infection is a mycobacterial infection.
19. The method of claim 1 , wherein the patient has bronchiectasis.
20. The method of claim 13 , wherein the pulmonary infection is a mycobacterial infection.
21. The method of claim 13 , wherein the pulmonary infection is an intracellular pulmonary infection.
22. The method of claim 13 , wherein the patient has bronchiectasis.
23. The method of claim 1 , wherein the inhalation delivery device is a nebulizer.
24. The method of claim 7 , wherein the quinolone antibiotic agent is ciprofloxacin.
25. The method of claim 13 , wherein the inhalation delivery device is a nebulizer.
26. The method of claim 22 , wherein the pulmonary infection is a Pseudomonas aeruginosa infection.