Aerosol delivery of liposome-encapsulated ciprofloxacin: aerosol characterization and efficacy against Francisella tularensis infection in mice.

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.

Liposome potentiation of humoral immune response to lipopolysaccharide and O-polysaccharide antigens of Brucella abortus.

Liposomes were evaluated for their effectiveness as vaccine carriers in the potentiation of the mouse humoral response to the lipopolysaccharide (LPS) and O-polysaccharide (OPS) antigens of Brucella abortus. LPS and OPS were extracted from a pathogenic strain of B. abortus and were encapsulated within multilamellar vesicles. Groups of mice, immunized with liposome-encapsulated and free LPS or OPS, were bled weekly and the specific IgM and IgG levels in the sera were determined by an indirect fluorogenic enzyme-linked immunosorbent assay. Humoral response to these antigens were found to be dose-dependent. Mice immunized with LPS and OPS encapsulated within liposomes were found to have significantly higher IgG levels than mice immunized with free LPS and OPS. In addition, the antibody levels in mice that were immunized with liposome-encapsulated LPS and OPS were more sustained and remained at elevated levels--even after 5 weeks post immunization. As expected, OPS was found to be less immunogenic than LPS, but multiple injections of OPS encapsulated within liposomes greatly improved the immunogenicity. These results indicate that the humoral response to LPS and OPS of B. abortus can be enhanced when these antigens are encapsulated within liposomes.

Immune response of the mouse to gram-negative bacterial outer membrane extracts as assessed with monoclonal antibodies.

Neisseria meningitidis outer membrane extracts of known serotype antigens as well as isolates from a linear carriage study were used to immunize mice for subsequent production of monoclonal antibodies. As well, membrane extracts from one strain of Pseudomonas aeruginosa, serotype M, were used. The degree of specificity of the resulting monoclonal antibodies to the two genera differed markedly when tested with known serotype antigens. That is, antibody from a given clone reacting with more than one serotype specificity was a more frequent occurrence among clones resulting from the Pseudomonas fusion. Preexisting "natural" antibody to several Pseudomonas species is considered at least partially responsible for the diversity of the response to this genus. Evidence is presented for the divergence of specificity with time after immunization with Neisseria.

Type-specific antigens of Neisseria meningitidis serogroup A.

By using Ouchterlony immunodiffusion techniques, we defined three unique antigenic determinants (A1, A2, and A3) among six isolates of Neisseria meningitidis serogroup A. Two of these determinants (A2 and A3) were identified as lipopolysaccharides in nature and were not found to occur on the serogroup B strains of N. meningitidis that we examined. The A1 determinant commonly occurred among the serogroup B strains and was identified as a protein determinant.