Abstract
Cyclosporin A (CsA)-dilauroylphosphatidylcholine (DLPC) liposome aerosol was evaluated for potential toxicity in a 28-day, acute toxicity study in rats. Rats of both sexes were housed in a nose-only chamber and exposed to aerosols of room air, water, DLPC liposomes (37.5 mg DLPC/ml in reservoir) or CsA-DLPC liposomes (5 mg CsA/ml and 37.5 mg DLPC in reservoir; 75.4 g CsA/L aerosol) generated by an AeroTech II nebulizer for 1 h each day for 28 consecutive days. The estimated retained dose of CsA was 1.58 mg CsA/kg body weight. The rats were monitored during the exposure period and for 2 wk after for body or organ weights, hematology, clinical chemistry, gross lesions, and histopathology of lungs, kidney, and liver. There were no differences for any of the parameters in any of the four exposure groups at any time point except for histopathology. These examinations revealed widespread chronic inflammatory lesions in all groups throughout the test period. These lesions were not associated with exposure to any of the test materials. The etiology of the pulmonary inflammation is unknown. The inflammatory lesions consisted of interstitial, perivascular, peribronchiolar, and alveolar cellular infiltrates that progressed to an organizing alveolitis with Type 2 cell hyperplasia and interstitial fibrosis. Lung lesions were observed in all experimental groups at all time points examined. The degree of severity of inflammatory lesions in the lungs increased with time through day 29 in all groups. Two weeks after final exposure to the test compounds (day 42), the average increase in severity and total number of lesions in all lobes were significantly less in the CsA-DLPC liposome-treated group (p < .04) and borderline in the DLPC group. Thus, DLPC and CsA-DLPC liposomes had no detectable adverse effects after daily inhalations over a period of 28 days, and there was a possible beneficial effect of CsA and possibly of DLPC against an opportunistic pulmonary pathogen in the rats that preexisted the aerosol exposures. </abs>
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
