Oxygen Radical-Mediated Pulmonary Toxicity Induced by Some Cationic Liposomes

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

doi:10.1023/a:1007504613351

Cited by 349Nanoparticle-Based Drug DeliveryInhalation and Respiratory Drug DeliveryRNA Interference and Gene Delivery

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Oxygen Radical-Mediated Pulmonary Toxicity Induced by Some Cationic Liposomes

Dokka, Sujatha, Toledo, David, Shi, Xianglin, Castranova, Vincent, Rojanasakul, Yon·2000·Pharmaceutical Research

DOI 10.1023/a:1007504613351

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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.

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Authors: Dokka, S., Toledo, D., Shi, X., Castranova, V., & Rojanasakul, Y.
Affiliations: West Virginia University (US)
National Institute for Occupational Safety and Health (US)
Corresponding author: Rojanasakul, Yon
ORCID: Shi, Xianglin
Rojanasakul, Yon
Venue: Pharmaceutical Research
Publisher: Springer Science and Business Media LLC
Published: 2000-05
Volume: 17
Issue: 5
Pages: 521-525
ISSN: 0724-8741 (ISSN-L)
1573-904X
DOI: 10.1023/a:1007504613351
OpenAlex: W1580639099
Cited by: 349
References: 14
Citations by year: 2026: 12 · 2025: 8 · 2024: 19 · 2023: 25 · 2022: 17 · 2021: 18 · 2020: 6 · 2019: 16 · 2018: 19 · 2017: 17 · 2016: 17 · 2015: 26 · 2014: 21 · 2013: 19 · 2012: 18
FWCI: 2.92
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Pharmaceutical Research (publishedVersion)
PubMed (publishedVersion)
Funders: West Virginia University
National Institutes of Health (1r15hl062959-01)
National Heart, Lung, and Blood Institute (HL-62959)
National Institute for Occupational Safety and Health
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords: cationic liposomes, pulmonary toxicity, reactive oxygen species, lipofectamine, DOTAP, liposome charge, respiratory burst, lung inflammation, liposomal gene delivery, chemiluminescence
MeSH terms: Animals, Bronchoalveolar Lavage Fluid, Cations, Cyclic N-Oxides, L-Lactate Dehydrogenase, Liposomes, Luminescent Measurements, Lung Diseases, Male, Mice, Inbred BALB C, Nitrogen Oxides, Free Radical Scavengers, Reactive Oxygen Species, Mice

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Oxygen Radical-Mediated Pulmonary Toxicity Induced by Some Cationic Liposomes

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