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Comparison of lung accumulation of cationic liposomes in normal rats and LPS-treated rats

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Abstract

Objective

Cationic liposomes have been shown to target angiogenic endothelial cells in lungs and joints with evidence of chronic inflammation. We sought to determine whether cationic liposomes accumulate in acutely inflamed lung tissue.

Subjects, treatment and methods

Acute lung injury was induced by intratracheal instillation of lipopolysaccharide (LPS) in Sprague Dawley rats. The controls received saline. Following instillation, the rats were ventilated for 5 h. Four hours after LPS-instillation each rat received rhodamine-labeled, cationic liposomes intravenously. The liposomes were allowed to circulate for 1 h. Thereafter, a bronchoalveolar lavage (BAL) was done and the lungs were perfused with saline and formalin. Accumulation of liposomes was assessed by quantitative confocal microscopy and determination of rhodamine-content in lung tissue.

Results

LPS induced a significant increase in BAL white blood cell count (3,444 ± 1,420 vs. 1,314 ± 906*103/μl) and cytokines (IL-1β: 145.57 vs. 51.94 pg/ml; TNF-α: 3,467.5 vs. 42.1 pg/ml) as compared to controls. Cationic liposomes exhibited an accumulation up to twofold in the inflamed lung tissue as compared to healthy lungs (fluorescent pixels 2.93 vs. 1.90(%)).

Conclusions

Our findings indicate that cationic liposomes accumulate in the acutely inflamed lung tissue. This uptake raises the possibility of using cationic liposomes to direct diagnostic/therapeutic agents selectively to the sites of acute inflammation in the lung.

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Abbreviations

ALI:

Acute lung injury

ARDS:

Acute respiratory distress syndrome

BAL:

Bronchoalveolar lavage

LPS:

Lipopolysaccharide from E. coli

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Acknowledgments

This work was supported by a grant in 2007 from the Bavarian Research Fund.

Author information

Authors and Affiliations

  1. Division of Neonatology, University Children’s Hospital, Perinatal Center, Ludwig-Maximilian-University Munich, Grosshadern, Marchioninistr.15, 81377, Munich, Germany

    Susanne Herber-Jonat, Rashmi Mittal, Stefan Gsinn & Andreas Schulze

  2. Division of Research, MediGene AG, Martinsried, Germany

    Hermann Bohnenkamp & Eric Guenzi

Authors
  1. Susanne Herber-Jonat
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  2. Rashmi Mittal
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  3. Stefan Gsinn
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  4. Hermann Bohnenkamp
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  5. Eric Guenzi
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  6. Andreas Schulze
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Corresponding author

Correspondence to Susanne Herber-Jonat.

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Responsible Editor: Michael Parnham.

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Herber-Jonat, S., Mittal, R., Gsinn, S. et al. Comparison of lung accumulation of cationic liposomes in normal rats and LPS-treated rats. Inflamm. Res. 60, 245–253 (2011). https://doi.org/10.1007/s00011-010-0260-y

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  • DOI: https://doi.org/10.1007/s00011-010-0260-y

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