The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Oxygen Radical-Mediated Pulmonary Toxicity Induced by Some Cationic Liposomes
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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“Cationic and ionizable lipids have also been reported to stimulate the secretion of pro-inflammatory cytokines and reactive oxygen species170–173.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [171]
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Metadata
- 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
- Venue
- Pharmaceutical Research
- Published
- 2000-05
- Volume
- 17
- Issue
- 5
- Pages
- 521-525
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- 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
- 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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