In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules

• Published in: International journal of nanomedicine Vol. 13; pp. 5159 - 5172
• Main Authors: Karabasz, Alicja, Szczepanowicz, Krzysztof, Cierniak, Agnieszka, Bereta, Joanna, Bzowska, Monika
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Adsorption; Amino acids; Animal experimentation; Animals; Antioxidants (Nutrients); Biochemistry; Biological activity; Biomedical materials; Cell Death - drug effects; Cytotoxicity; DNA; DNA Damage; Drug delivery systems; Endothelium; Enzymes; Erythrocytes - drug effects; Erythrocytes - metabolism; Gene expression; Genes; Genetic research; genotoxicity; Glutamate; Glycols (Class of compounds); Hemolysis; Hemolysis - drug effects; Hep G2 Cells; Humans; Inflammation - pathology; Kinases; layer-by-layer; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lysine; Mice; Mutagens - toxicity; Nanocapsules - toxicity; Nanoemulsions; Nanomaterials; Nanoparticles; nanotoxicity; Nitric oxide; Nitrogen oxides; Original Research; Oxidative stress; Oxidative Stress - drug effects; Particle Size; polyelectrolyte nanocapsules; Polyelectrolytes - chemical synthesis; Polyelectrolytes - toxicity; Polyethylene glycol; Polyethylene Glycols - chemistry; Polymer industry; Polyols; Quantum dots; Toxicity; Toxicity Tests; Tumor necrosis factor-TNF; Poland; genotoxicity; layer-by-layer; nanotoxicity; polyelectrolyte nanocapsules; oxidative stress
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S169120

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. 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. 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. 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.