Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes

Sujatha Dokka, David Toledo, Xianglin Shi, Vincent Castranova, Yon Rojanasakul

Research output: Contribution to journalArticlepeer-review

331 Scopus citations

Abstract

Purpose. The objectives of this study are to investigate the toxicity associated with polycationic liposomes and to elucidate the underlying mechanism. We tested the hypothesis that the positive charge of liposomes is a key determinant of toxicity by testing differently charged liposomes in mice. Methods. Differently charged liposomal systems including cationic liposomes, LipofectAMINE and DOTAP, and neutral and negative liposomes were evaluated for their toxicity after pulmonary administration in mice. LDH assay and differential cell counts were performed to measure toxicity and pulmonary inflammation, respectively. Reactive oxygen intermediates (ROI) were assessed by chemiluminescence. Results. Instillation of cationic liposomes elicited dose-dependent toxicity and pulmonary inflammation. This effect was more pronounced with the multivalent cationic liposome LipofectAMINE as compared to the monovalent cationic DOTAP. Neutral and negative liposomes did not exhibit lung toxicity. Toxicity associated with cationic liposomes correlated with the oxidative burst induced by the liposomes. LipofectAMINE induced a dose-dependent increase in ROI generation. This effect was less pronounced with DOTAP and absent with neutral and negative liposomes. Conclusions. ROI play a key role in cationic lipid- mediated toxicity. Polyvalent cationic liposomes cause a release of ROI which are responsible for the pulmonary toxicity.

Original languageEnglish
Pages (from-to)521-525
Number of pages5
JournalPharmaceutical Research
Volume17
Issue number5
DOIs
StatePublished - 2000

Bibliographical note

Funding Information:
This work was supported in part by the National Institutes of Health Grant HL62959 and by the National Institute for Occupational Safety and Health.

Keywords

  • Cationic liposomes
  • Charge
  • Reactive oxygen intermediates
  • Toxicity

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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