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Drug Res (Stuttg) 2017; 67(11): 661-672
DOI: 10.1055/s-0043-115123
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

Jasmina Hadžiabdić
1   Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
,
Nevenka Kopjar
2   Institute for Medical Research and Occupational Health, Zagreb, Croatia
,
Davor Želježić
2   Institute for Medical Research and Occupational Health, Zagreb, Croatia
,
Selma Špirtović-Halilović
3   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
,
Davorka Završnik
3   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
› Author Affiliations
Further Information

Publication History

received 17 February 2017

accepted 27 June 2017

Publication Date:
19 July 2017 (online)

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Abstract

Background 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 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.

Methods 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.

Results Neither one of the diazepam, complexed nor non-complexed, in given concentrations showed genotoxicity, induced genetic damage or loss of genetic material.

Conclusions 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.

Key words

anxiolytic drugs - apoptosis - drug delivery - cytokines
 

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