Comparative study of cytotoxicity and genotoxicity of commercial Jeffamines® and polyethylenimine in CHO-K1 cells.
Jeffamines®are a family of polymers containing primary amine groups attached to the extremities of polyether backbone which can be used as biomaterials. They have been used in combination with polyethylenimine (PEI) to improve biocompatibility in drug and gene delivery systems. Despite these facts, very few studies have been done on cytotoxicity and genotoxicity of pure Jeffamines®or compared with PEI. The present study aimed to evaluate and compare the cytotoxic and genotoxic effects of Jeffamines®and PEI in CHO-K1 cells. Specifically, polypropylene oxide 2000 (PPO 2000, Jeffamine®D series), polyethylene oxide 1900 (PEO 1900, Jeffamine®ED series), branched 25 kDa PEI, and linear 20 kDa PEI were evaluated at different concentrations. Cell viability and proliferation were assessed by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and 5-bromo-2'-deoxyuridine (BrdU) assays, respectively. Genotoxicity was evaluated using single cell gel electrophoresis assay and the cytokinesis-blocked micronucleus assay. PPO 2000 was the most cytotoxic Jeffamine®, whereas PEO 1900 did not caused significant cell death at any tested concentration. Branched PEI was more cytotoxic than linear PEI (LPEI) and both were more cytotoxic than Jeffamines®. Only PPO 2000 induced DNA damage when evaluated in comet assay probably due to its cytotoxicity. PPO 2000, PEO 1900, and PEI did not increase the frequency of micronuclei when tested at sub-cytotoxic concentrations. This work provides new insights about biocompatibility of Jeffamines®and PEI and suggests the genotoxicological safety for further investigations of PEO 1900 in drug and gene delivery systems. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 742-750, 2018.
Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, SP, Brazil.
Leniher
L
Castan
Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, SP, Brazil.
Cristiano
C
José da Silva
Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, SP, Brazil.
Eduardo
E
Ferreira Molina
Núcleo de Pesquisas em Ciências Exatas e Tecnológicas, Universidade de Franca, Franca, SP, Brazil.
Raquel
R
Alves Dos Santos
D000818:Animals; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D004249:DNA Damage; D004353:Drug Evaluation, Preclinical; D011094:Polyethyleneimine / Q000009:adverse effects / Q000494:pharmacology; D011108:Polymers / Q000009:adverse effects / Q000494:pharmacology; D011409:Propylene Glycols / Q000009:adverse effects / Q000494:pharmacology
D011108:Polymers; D011409:Propylene Glycols; C012504:polypropylene glycol; D011094:Polyethyleneimine
biocompatibility; cationic polymers; cytotoxicity; genotoxicity; non-viral vectors