title: The enhanced inhibitory effect of different antitumor agents in self-microemulsifying drug delivery systems on human cervical cancer HeLa cells.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen 4032, Hungary. ujhelyi.zoltan@pharm.unideb.hu.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Ujhelyi
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen 4032, Hungary. azin.kalantari@yahoo.com.
authors.forename: Azin
authors.initials: A
authors.lastname: Kalantari
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen 4032, Hungary. vecsernyes.miklos@pharm.unideb.hu.
authors.forename: Miklós
authors.initials: M
authors.lastname: Vecsernyés
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen 4032, Hungary. roka.eszter@pharm.unideb.hu.
authors.forename: Eszter
authors.initials: E
authors.lastname: Róka
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen 4032, Hungary. fenyvesi.ferenc@pharm.unideb.hu.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fenyvesi
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary. pokar@med.unideb.hu.
authors.forename: Róbert
authors.initials: R
authors.lastname: Póka
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary. bence.kozma@med.unideb.hu.
authors.forename: Bence
authors.initials: B
authors.lastname: Kozma
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen 4032, Hungary. bacskay.ildiko@pharm.unideb.hu.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Bácskay
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D005260:Female; D006367:HeLa Cells; D006801:Humans; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions
keywords: HeLa; SMEDDS; bleomycin; cisplatin; ifosfamide