Abstract
The aerosol delivery of liposome-encapsulated ciprofloxacin by using 12 commercially available jet nebulizers was evaluated in this study. Aerosol particles containing liposome-encapsulated ciprofloxacin generated by the nebulizers were analyzed with a laser aerodynamic particle sizer. Mean mass aerodynamic diameters (MMADs) and geometric standard deviations (GSDs) were determined, and the drug contents of the sampling filters from each run onto which aerosolized liposome-encapsulated ciprofloxacin had been deposited were analyzed spectrophotometrically. The aerosol particles of liposome-encapsulated ciprofloxacin generated by these nebulizers ranged from 1.94 to 3.5 microm, with GSDs ranging from 1.51 to 1.84 microm. The drug contents of the sampling filters exposed for 1 min to aerosolized liposome-encapsulated ciprofloxacin range from 12.7 to 40.5 microg/ml (0.06 to 0.2 mg/filter). By using the nebulizer selected on the basis of most desirable MMADs, particle counts, and drug deposition, aerosolized liposome-encapsulated ciprofloxacin was used for the treatment of mice infected with 10 times the 50% lethal dose of Francisella tularensis. All mice treated with aerosolized liposome-encapsulated ciprofloxacin survived the infection, while all ciprofloxacin-treated or untreated control mice succumbed to the infection (P < 0.001). These results suggest that aerosol delivery of liposome-encapsulated ciprofloxacin to the lower respiratory tract is feasible and that it may provide an effective therapy for the treatment of respiratory tract infections.
Full Text
The Full Text of this article is available as a PDF (170.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Atmar R. L., Greenberg S. B., Quarles J. M., Wilson S. Z., Tyler B., Feldman S., Couch R. B. Safety and pharmacokinetics of rimantadine small-particle aerosol. Antimicrob Agents Chemother. 1990 Nov;34(11):2228–2233. doi: 10.1128/aac.34.11.2228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chin N. X., Neu H. C. Ciprofloxacin, a quinolone carboxylic acid compound active against aerobic and anaerobic bacteria. Antimicrob Agents Chemother. 1984 Mar;25(3):319–326. doi: 10.1128/aac.25.3.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clarke S. W., Newman S. P. Therapeutic aerosols 2--Drugs available by the inhaled route. Thorax. 1984 Jan;39(1):1–7. doi: 10.1136/thx.39.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Debs R. J., Straubinger R. M., Brunette E. N., Lin J. M., Lin E. J., Montgomery A. B., Friend D. S., Papahadjopoulos D. P. Selective enhancement of pentamidine uptake in the lung by aerosolization and delivery in liposomes. Am Rev Respir Dis. 1987 Mar;135(3):731–737. doi: 10.1164/arrd.1987.135.3.731. [DOI] [PubMed] [Google Scholar]
- Di Ninno V. L., Cherwanogrodzky J. W., Wong J. P. Liposome-encapsulated ciprofloxacin is effective in the protection and treatment of BALB/c mice against Francisella tularensis. J Infect Dis. 1993 Sep;168(3):793–794. doi: 10.1093/infdis/168.3.793. [DOI] [PubMed] [Google Scholar]
- Fenlon C. H., Cynamon M. H. Comparative in vitro activities of ciprofloxacin and other 4-quinolones against Mycobacterium tuberculosis and Mycobacterium intracellulare. Antimicrob Agents Chemother. 1986 Mar;29(3):386–388. doi: 10.1128/aac.29.3.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fortier A. H., Slayter M. V., Ziemba R., Meltzer M. S., Nacy C. A. Live vaccine strain of Francisella tularensis: infection and immunity in mice. Infect Immun. 1991 Sep;59(9):2922–2928. doi: 10.1128/iai.59.9.2922-2928.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gay J. D., DeYoung D. R., Roberts G. D. In vitro activities of norfloxacin and ciprofloxacin against Mycobacterium tuberculosis, M. avium complex, M. chelonei, M. fortuitum, and M. kansasii. Antimicrob Agents Chemother. 1984 Jul;26(1):94–96. doi: 10.1128/aac.26.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilbert B. E., Six H. R., Wilson S. Z., Wyde P. R., Knight V. Small particle aerosols of enviroxime-containing liposomes. Antiviral Res. 1988 Sep;9(6):355–365. doi: 10.1016/0166-3542(88)90037-x. [DOI] [PubMed] [Google Scholar]
- Gilbert B. E., Wyde P. R., Wilson S. Z. Aerosolized liposomal amphotericin B for treatment of pulmonary and systemic Cryptococcus neoformans infections in mice. Antimicrob Agents Chemother. 1992 Jul;36(7):1466–1471. doi: 10.1128/aac.36.7.1466. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gonzalez-Rothi R. J., Straub L., Cacace J. L., Schreier H. Liposomes and pulmonary alveolar macrophages: functional and morphologic interactions. Exp Lung Res. 1991 Jul-Aug;17(4):687–705. doi: 10.3109/01902149109062873. [DOI] [PubMed] [Google Scholar]
- Heifets L. B., Lindholm-Levy P. J. Bacteriostatic and bactericidal activity of ciprofloxacin and ofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex. Tubercle. 1987 Dec;68(4):267–276. doi: 10.1016/0041-3879(87)90067-5. [DOI] [PubMed] [Google Scholar]
- Hodson M. E., Penketh A. R., Batten J. C. Aerosol carbenicillin and gentamicin treatment of Pseudomonas aeruginosa infection in patients with cystic fibrosis. Lancet. 1981 Nov 21;2(8256):1137–1139. doi: 10.1016/s0140-6736(81)90588-2. [DOI] [PubMed] [Google Scholar]
- Knight V., Yu C. P., Gilbert B. E., Divine G. W. Estimating the dosage of ribavirin aerosol according to age and other variables. J Infect Dis. 1988 Aug;158(2):443–448. doi: 10.1093/infdis/158.2.443. [DOI] [PubMed] [Google Scholar]
- Magallanes M., Dijkstra J., Fierer J. Liposome-incorporated ciprofloxacin in treatment of murine salmonellosis. Antimicrob Agents Chemother. 1993 Nov;37(11):2293–2297. doi: 10.1128/aac.37.11.2293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mehta R. T., Keyhani A., McQueen T. J., Rosenbaum B., Rolston K. V., Tarrand J. J. In vitro activities of free and liposomal drugs against Mycobacterium avium-M. intracellulare complex and M. tuberculosis. Antimicrob Agents Chemother. 1993 Dec;37(12):2584–2587. doi: 10.1128/aac.37.12.2584. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montgomery A. B., Debs R. J., Luce J. M., Corkery K. J., Turner J., Brunette E. N., Lin E. T., Hopewell P. C. Selective delivery of pentamidine to the lung by aerosol. Am Rev Respir Dis. 1988 Feb;137(2):477–478. doi: 10.1164/ajrccm/137.2.477. [DOI] [PubMed] [Google Scholar]
- O'Doherty M. J., Thomas S., Page C., Barlow D., Bradbeer C., Nunan T. O., Bateman N. T. Differences in relative efficiency of nebulisers for pentamidine administration. Lancet. 1988 Dec 3;2(8623):1283–1286. doi: 10.1016/s0140-6736(88)92894-2. [DOI] [PubMed] [Google Scholar]
- Oh Y. K., Nix D. E., Straubinger R. M. Formulation and efficacy of liposome-encapsulated antibiotics for therapy of intracellular Mycobacterium avium infection. Antimicrob Agents Chemother. 1995 Sep;39(9):2104–2111. doi: 10.1128/aac.39.9.2104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quentin R., Koubaa N., Cattier B., Gavignet M., Goudeau A. In vitro activities of five new quinolones against 88 genital and neonatal Haemophilus isolates. Antimicrob Agents Chemother. 1988 Jan;32(1):147–149. doi: 10.1128/aac.32.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rao S., Wilson D. B., Brooks R. C., Sproule B. J. Acute effects of nebulization of N-acetylcysteine on pulmonary mechanics and gas exchange. Am Rev Respir Dis. 1970 Jul;102(1):17–22. doi: 10.1164/arrd.1970.102.1.17. [DOI] [PubMed] [Google Scholar]
- Roy C., Foz A., Segura C., Tirado M., Teixell M., Teruel D. Activity of ciprofloxacin (BAYo 9867) against Pseudomonas aeruginosa and ampicillin-resistant Enterobacteriaceae. Infection. 1983 Nov-Dec;11(6):326–328. doi: 10.1007/BF01641358. [DOI] [PubMed] [Google Scholar]
- Taylor K. M., Taylor G., Kellaway I. W., Stevens J. The influence of liposomal encapsulation on sodium cromoglycate pharmacokinetics in man. Pharm Res. 1989 Jul;6(7):633–636. doi: 10.1023/a:1015917918130. [DOI] [PubMed] [Google Scholar]
- Waldrep J. C., Keyhani K., Black M., Knight V. Operating characteristics of 18 different continuous-flow jet nebulizers with beclomethasone dipropionate liposome aerosol. Chest. 1994 Jan;105(1):106–110. doi: 10.1378/chest.105.1.106. [DOI] [PubMed] [Google Scholar]
- Wong J. P., Stadnyk L. L., Saravolac E. G. Enhanced protection against respiratory influenza A infection in mice by liposome-encapsulated antibody. Immunology. 1994 Feb;81(2):280–284. [PMC free article] [PubMed] [Google Scholar]