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Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles

The rapid growth of nanoparticle-based therapeutics has underpinned significant developments in nanomedicine, which aim to overcome the limitations imposed by conventional therapies. Establishing the safety of new nanoparticle formulations is the first important step on the pathway to clinical trans...

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Autores principales: Michael, Praveesuda L., Lam, Yuen Ting, Hung, Juichien, Tan, Richard P., Santos, Miguel, Wise, Steven G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145910/
https://www.ncbi.nlm.nih.gov/pubmed/33947114
http://dx.doi.org/10.3390/nano11051176
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author Michael, Praveesuda L.
Lam, Yuen Ting
Hung, Juichien
Tan, Richard P.
Santos, Miguel
Wise, Steven G.
author_facet Michael, Praveesuda L.
Lam, Yuen Ting
Hung, Juichien
Tan, Richard P.
Santos, Miguel
Wise, Steven G.
author_sort Michael, Praveesuda L.
collection PubMed
description The rapid growth of nanoparticle-based therapeutics has underpinned significant developments in nanomedicine, which aim to overcome the limitations imposed by conventional therapies. Establishing the safety of new nanoparticle formulations is the first important step on the pathway to clinical translation. We have recently shown that plasma-polymerized nanoparticles (PPNs) are highly efficient nanocarriers and a viable, cost-effective alternative to conventional chemically synthesized nanoparticles. Here, we present the first comprehensive toxicity and biosafety study of PPNs using both established in vitro cell models and in vivo models. Overall, we show that PPNs were extremely well tolerated by all the cell types tested, significantly outperforming commercially available lipid-based nanoparticles (lipofectamine) used at the manufacturer’s recommended dosage. Supporting the in vitro data, the systemic toxicity of PPNs was negligible in BALB/c mice following acute and repeated tail-vein intravenous injections. PPNs were remarkably well tolerated in mice without any evidence of behavioral changes, weight loss, significant changes to the hematological profile, or signs of histological damage in tissues. PPNs were tolerated at extremely high doses without animal mortality observed at 6000 mg/kg and 48,000 mg/kg for acute and repeated-injection regimens, respectively. Our findings demonstrate the safety of PPNs in biological systems, adding to their future potential in biomedical applications.
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spelling pubmed-81459102021-05-26 Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles Michael, Praveesuda L. Lam, Yuen Ting Hung, Juichien Tan, Richard P. Santos, Miguel Wise, Steven G. Nanomaterials (Basel) Article The rapid growth of nanoparticle-based therapeutics has underpinned significant developments in nanomedicine, which aim to overcome the limitations imposed by conventional therapies. Establishing the safety of new nanoparticle formulations is the first important step on the pathway to clinical translation. We have recently shown that plasma-polymerized nanoparticles (PPNs) are highly efficient nanocarriers and a viable, cost-effective alternative to conventional chemically synthesized nanoparticles. Here, we present the first comprehensive toxicity and biosafety study of PPNs using both established in vitro cell models and in vivo models. Overall, we show that PPNs were extremely well tolerated by all the cell types tested, significantly outperforming commercially available lipid-based nanoparticles (lipofectamine) used at the manufacturer’s recommended dosage. Supporting the in vitro data, the systemic toxicity of PPNs was negligible in BALB/c mice following acute and repeated tail-vein intravenous injections. PPNs were remarkably well tolerated in mice without any evidence of behavioral changes, weight loss, significant changes to the hematological profile, or signs of histological damage in tissues. PPNs were tolerated at extremely high doses without animal mortality observed at 6000 mg/kg and 48,000 mg/kg for acute and repeated-injection regimens, respectively. Our findings demonstrate the safety of PPNs in biological systems, adding to their future potential in biomedical applications. MDPI 2021-04-29 /pmc/articles/PMC8145910/ /pubmed/33947114 http://dx.doi.org/10.3390/nano11051176 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Michael, Praveesuda L.
Lam, Yuen Ting
Hung, Juichien
Tan, Richard P.
Santos, Miguel
Wise, Steven G.
Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles
title Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles
title_full Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles
title_fullStr Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles
title_full_unstemmed Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles
title_short Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles
title_sort comprehensive evaluation of the toxicity and biosafety of plasma polymerized nanoparticles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145910/
https://www.ncbi.nlm.nih.gov/pubmed/33947114
http://dx.doi.org/10.3390/nano11051176
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