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  • Title: Characterization and administration of cyclosporine liposomes as a small-particle aerosol.
    Author: Gilbert BE, Wilson SZ, Garcon NM, Wyde PR, Knight V.
    Journal: Transplantation; 1993 Oct; 56(4):974-7. PubMed ID: 8212222.
    Abstract:
    Systemically administered CsA has not consistently suppressed the pulmonary immunoreactivity that leads to rejection in lung transplant patients. Pulmonary T cells from patients given CsA systemically still retain their immunoreactivity, which can be suppressed with added CsA. Direct application of CsA by aerosol to the respiratory epithelium should achieve high lung concentrations with minimum systemic effects. In the present study, CsA was most efficiently incorporated into liposomes composed of egg yolk phosphatidylcholine at a molar ratio of CsA to egg yolk phosphatidylcholine of 1:20. These CsA liposomes retained their biological activity and were as effective as free CsA in the suppression of anti-CD3-stimulated [3H]thymidine incorporation by mouse spleen cells. The generation of a small-particle aerosol of CsA liposomes had no effect on this biological activity. CsA liposome aerosol particles have a mass median aerodynamic diameter of 2 microns, which allows for distribution of drug throughout the respiratory tract. Quantitation of CsA in the lungs and blood of mice exposed to CsA liposome aerosols for 4 days showed that as little as 15 min daily (0.11 mg/kg/day) was sufficient to achieve an estimated concentration of CsA in respiratory secretions of 6 micrograms/ml without detectable blood levels. Thus, CsA liposomes can be produced and aerosolized that achieve pulmonary concentrations with sufficient immunosuppressive activity to be effective in the treatment of lung diseases.
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