Cytogenotoxicity of Inclusion Complexes of Diazepam with 2-Hydroxypropyl-β-cyclodextrin

• Published in: Drug research Vol. 67; no. 11; p. 661
• Main Authors: Hadžiabdić, Jasmina, Kopjar, Nevenka, Želježić, Davor, Špirtović-Halilović, Selma, Završnik, Davorka
• Format: Journal Article
• Language: English
• Published: Germany 01-11-2017
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin - chemistry; Cell Cycle - drug effects; Cell Nucleus - drug effects; Cell Proliferation - drug effects; Chemistry, Pharmaceutical - methods; Cytochalasin B - pharmacology; Cytogenetic Analysis - methods; Cytoplasm - drug effects; Diazepam - chemistry; Diazepam - toxicity; Humans; Hypnotics and Sedatives - chemistry; Hypnotics and Sedatives - toxicity; Lymphocytes - drug effects; Micronucleus Tests - methods; Solubility
• ISSN: 2194-9387
• DOI: 10.1055/s-0043-115123

Diazepam, as one of the most frequent prescribed drug from 1,4-benzodiazepine group, has certain limitations in pharmaceutical technology due to its poor solubility in water. By forming inclusion complexes with 2-hydroxypropyl-β-cyclodextrin, diazepam's biopharmaceutical properties can be greatly improved.
Aim of this research was to in vitro evaluate genotoxicity of prepared novel complexes of diazepam and their influence on proliferation of human peripheral blood lymphocytes.
For identification of possible genotoxicity of diazepam inclusion complexes, cytokinesis-block micronucleus assay has been chosen. Evaluated concentrations of two diazepam inclusion complexes were 0.2 µg/mL, 0.5 µg/mL and 1.0 µg/mL in cell culture. For a reference, in vitro cytogenotoxicity evaluation of diazepam alone has been conducted as well.
Neither one of the diazepam, complexed nor non-complexed, in given concentrations showed genotoxicity, induced genetic damage or loss of genetic material.
Nuclear division index values, as indicators of cytostaticity and cytotoxicity suggested that investigated inclusion diazepam complexes induced accelerated proliferation of human peripheral blood lymphocytes in vitro, therefore possibly shortening the duration and dynamics of the cell cycle.