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Open AccessArticle

The Enhanced Inhibitory Effect of Different Antitumor Agents in Self-Microemulsifying Drug Delivery Systems on Human Cervical Cancer HeLa Cells

Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen 4032, Hungary
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Thomas Rades, Holger Grohganz and Korbinian Löbmann
Molecules 2015, 20(7), 13226-13239;
Received: 5 May 2015 / Revised: 6 July 2015 / Accepted: 7 July 2015 / Published: 21 July 2015
(This article belongs to the Collection Poorly Soluble Drugs)
The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS was also investigated. Their IC50 values were determined. HeLa cells were treated by different concentrations of cisplatin, bleomycin and ifosfamide alone and in various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell viability assay. Inflammation is a driving force that accelerates cancer development. The inhibitory effect of these antitumor agents has also been tested on HeLa cells in the presence of inflammatory mediators (IL-1-β, TNF-α) as an in vitro model of inflamed human cervix. Significant differences in the cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a concentration-dependent manner. The self-micro emulsifying system may potentiate the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of SMEDDS containing antitumor agents was decreased significantly in the presence of inflammatory mediators. According to our experiments, the optimal SMEDDS formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH 40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the effectiveness of SMEDDS containing antitumor agents. Our results might ensure useful data for development of optimal antitumor formulations. View Full-Text
Keywords: HeLa; bleomycin; ifosfamide; cisplatin; SMEDDS HeLa; bleomycin; ifosfamide; cisplatin; SMEDDS
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Ujhelyi, Z.; Kalantari, A.; Vecsernyés, M.; Róka, E.; Fenyvesi, F.; Póka, R.; Kozma, B.; Bácskay, I. The Enhanced Inhibitory Effect of Different Antitumor Agents in Self-Microemulsifying Drug Delivery Systems on Human Cervical Cancer HeLa Cells. Molecules 2015, 20, 13226-13239.

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