Evaluation of in vitro toxicity of peptide (N-acetyl-Leu-Gly-Leu-COOH)-substituted-β-cyclodextrin derivative, a novel drug carrier, in PC-12 cells

BACKGROUND: Cyclodextrins (CDs) have been shown to improve physicochemical and biopharmaceutical properties of drugs when low solubility and low safety limit their use in the pharmaceutical field. Recently, a new amphiphilic peptide-substituted-β-CD, hepta-(N-acetyl-Leu-Gly-Leu)-β-CD (hepta-(N-acetyl-LGL)-β-CD), is developed which exhibited good solubility, strong inclusion ability and an appropriate average molecular weight. However, there is limited information available about its toxic effects. This study was designed to evaluate cytotoxic effects of the hepta-(N-acetyl-LGL)-β-CD (50, 200, 400, and 800 μg/ml) on rat pheochromocytoma PC-12 cells. RESULTS: A significant reduction of cell viability with IC(50) values of 1115.0 μg/ml, 762.4 μg/ml, and 464.9 μg/ml at 6, 12, and 24 h post-treatment, respectively, as well as increased lipid peroxide levels and DNA damage were observed. CONCLUSIONS: In conclusion, hepta-(N-acetyl-Leu-Gly-Leu)-β-CD exhibit significant toxic properties at high concentrations, probably through induction of oxidative stress and genotoxicity.