In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules

Alicja Karabasz,1 Krzysztof Szczepanowicz,2 Agnieszka Cierniak,1,3 Joanna Bereta,1 Monika Bzowska1 1Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 2Jerzy Haber Institute of Catalysis and Surface Chemistry,...

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Autores principales:	Karabasz A, Szczepanowicz K, Cierniak A, Bereta J, Bzowska M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	polyelectrolyte nanocapsules layer-by-layer nanotoxicity oxidative stress genotoxicity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e02d9740706f4bb0862821f6bd4517d8
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spelling	oai:doaj.org-article:e02d9740706f4bb0862821f6bd4517d82021-12-02T11:21:13ZIn vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules1178-2013https://doaj.org/article/e02d9740706f4bb0862821f6bd4517d82018-09-01T00:00:00Zhttps://www.dovepress.com/in-vitro-toxicity-studies-of-biodegradable-polyelectrolyte-nanocapsule-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Alicja Karabasz,1 Krzysztof Szczepanowicz,2 Agnieszka Cierniak,1,3 Joanna Bereta,1 Monika Bzowska1 1Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 2Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Kraków, Poland; 3Department of Biochemistry, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Kraków University, Kraków, Poland Background: Toxicity of nanomaterials is one of the most important factors limiting their medical application. Evaluation of in vitro nanotoxicity allows for the identification and elimination of most of the toxic materials prior to animal testing. The current knowledge of the possible side effects of biodegradable nanomaterials, such as liposomes and polymeric organic nanoparticles, is limited. Previously, we developed a potential drug delivery system in the form of nanocapsules with polyelectrolyte, biodegradable shells consisting of poly-L-lysine and poly-L-glutamic acid (PGA), formed by the layer-by-layer adsorption technique. Methods: Hemolysis assay, viability tests, flow cytometry analysis of vascular cell adhesion molecule-1 expression on endothelium, analysis of nitric oxide production, measurement of intracellular reactive oxygen species levels, detection of antioxidant enzyme activity, and analysis of DNA damage with comet assay were performed to study the in vitro toxicity of nanocapsules. Results: In this work, we present the results of an in vitro analysis of toxicity of five-layer positively charged poly-L-lysine–terminated nanocapsules (NC5), six-layer negatively charged PGA-terminated nanocapsules (NC6) and five-layer PEGylated nanocapsules (NC5-PEG). PGA and polyethylene glycol (PEG) were used as two different “stealth” polymers. Of all the polyelectrolyte nanocapsules tested for blood compatibility, only cationic NC5 showed acute toxicity toward blood cells, expressed as hemolysis and aggregation. Neither NC6 nor NC5-PEG had proinflammatory activity evaluated through changes in the expression of NF-κB–dependent genes, iNOS and vascular cell adhesion molecule-1, induced oxidative stress, or promoted DNA damage in various cells. Conclusion: Our studies clearly indicate that PGA-coated (negatively charged) and PEGylated polyelectrolyte nanocapsules do not show in vitro toxicity, and their potential as a drug delivery system may be safely studied in vivo. Keywords: polyelectrolyte nanocapsules, layer-by-layer, nanotoxicity, oxidative stress, genotoxicityKarabasz ASzczepanowicz KCierniak ABereta JBzowska MDove Medical Pressarticlepolyelectrolyte nanocapsuleslayer-by-layernanotoxicityoxidative stressgenotoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 5159-5172 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	polyelectrolyte nanocapsules layer-by-layer nanotoxicity oxidative stress genotoxicity Medicine (General) R5-920
spellingShingle	polyelectrolyte nanocapsules layer-by-layer nanotoxicity oxidative stress genotoxicity Medicine (General) R5-920 Karabasz A Szczepanowicz K Cierniak A Bereta J Bzowska M In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules
description	Alicja Karabasz,1 Krzysztof Szczepanowicz,2 Agnieszka Cierniak,1,3 Joanna Bereta,1 Monika Bzowska1 1Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland; 2Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Kraków, Poland; 3Department of Biochemistry, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Kraków University, Kraków, Poland Background: Toxicity of nanomaterials is one of the most important factors limiting their medical application. Evaluation of in vitro nanotoxicity allows for the identification and elimination of most of the toxic materials prior to animal testing. The current knowledge of the possible side effects of biodegradable nanomaterials, such as liposomes and polymeric organic nanoparticles, is limited. Previously, we developed a potential drug delivery system in the form of nanocapsules with polyelectrolyte, biodegradable shells consisting of poly-L-lysine and poly-L-glutamic acid (PGA), formed by the layer-by-layer adsorption technique. Methods: Hemolysis assay, viability tests, flow cytometry analysis of vascular cell adhesion molecule-1 expression on endothelium, analysis of nitric oxide production, measurement of intracellular reactive oxygen species levels, detection of antioxidant enzyme activity, and analysis of DNA damage with comet assay were performed to study the in vitro toxicity of nanocapsules. Results: In this work, we present the results of an in vitro analysis of toxicity of five-layer positively charged poly-L-lysine–terminated nanocapsules (NC5), six-layer negatively charged PGA-terminated nanocapsules (NC6) and five-layer PEGylated nanocapsules (NC5-PEG). PGA and polyethylene glycol (PEG) were used as two different “stealth” polymers. Of all the polyelectrolyte nanocapsules tested for blood compatibility, only cationic NC5 showed acute toxicity toward blood cells, expressed as hemolysis and aggregation. Neither NC6 nor NC5-PEG had proinflammatory activity evaluated through changes in the expression of NF-κB–dependent genes, iNOS and vascular cell adhesion molecule-1, induced oxidative stress, or promoted DNA damage in various cells. Conclusion: Our studies clearly indicate that PGA-coated (negatively charged) and PEGylated polyelectrolyte nanocapsules do not show in vitro toxicity, and their potential as a drug delivery system may be safely studied in vivo. Keywords: polyelectrolyte nanocapsules, layer-by-layer, nanotoxicity, oxidative stress, genotoxicity
format	article
author	Karabasz A Szczepanowicz K Cierniak A Bereta J Bzowska M
author_facet	Karabasz A Szczepanowicz K Cierniak A Bereta J Bzowska M
author_sort	Karabasz A
title	In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules
title_short	In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules
title_full	In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules
title_fullStr	In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules
title_full_unstemmed	In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules
title_sort	in vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/e02d9740706f4bb0862821f6bd4517d8
work_keys_str_mv	AT karabasza invitrotoxicitystudiesofbiodegradablepolyelectrolytenanocapsules AT szczepanowiczk invitrotoxicitystudiesofbiodegradablepolyelectrolytenanocapsules AT cierniaka invitrotoxicitystudiesofbiodegradablepolyelectrolytenanocapsules AT beretaj invitrotoxicitystudiesofbiodegradablepolyelectrolytenanocapsules AT bzowskam invitrotoxicitystudiesofbiodegradablepolyelectrolytenanocapsules
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In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules

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