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

Introduction: Cyclodextrins (CDs) have been shown to improve physicochemical and biopharmaceuticalproperties of drugs when low solubility and low safety limit their use in the pharmaceutical field. Recently, anew 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 molecularweight. However, there is limited information available about its toxic effects.Method: 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 IC50 values of 1115.0 μg/ml, 762.4 μg/ml, and 464.9μg/ml at 6, 12, and 24 h post-treatment, respectively, as well as increased lipid peroxide levels and DNA damagewere observed.Conclusions: In conclusion, hepta-(N-acetyl-Leu-Gly-Leu)-β-CD exhibit significant toxic properties at highconcentrations, probably through induction of oxidative stress and genotoxicity.

Keywords:

Hepta-(N-acetyl-Leu-Gly-Leu)-β-CD , Lipid peroxidation , DNA damage , Oxidative stress , PC-12 cells