98-104 Baspinar LAJP 4353:Baspinar

Latin American Journal of Pharmacy
(formerly Acta Farmacéutica Bonaerense)
Lat. Am. J. Pharm. 35 (1): 98-104 (2016)
Regular article
Received: July 2, 2015
Revised version: September 10, 2015
Accepted: September 13, 2015
Hepatotoxicity, Acute Toxicity and Salmonella/Microsome
Mutagenicity Assay (Ames) of Imatinib Microemulsions
Yücel BAŞPINAR 1,2, Evren GUNDOGDU 3, Cinel KOKSAL 2,4, Hatice Y. KARASULU 5,
Nefise U. KARABAY YAVAŞOĞLU 2,4 & Ercüment KARASULU 2,6
1
Ege University, Faculty of Pharmacy, Department of Pharmaceutical Biotechnology,
35100, Izmir, Turkey.
2 Ege University, Center for Drug Research & Development
and Pharmacokinetic Applications, 35100, Izmir, Turkey.
3 Ege University, Faculty of Pharmacy, Department of Radiopharmacy, 35100, Izmir, Turkey.
4 Ege University, Faculty of Science, Department of Biology, 35100 Bornova, Izmir, Turkey
5 Ege University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 35100, Izmir, Turkey.
6 Ege University, Faculty of Pharmacy, Department of Biopharmaceutics
and Pharmacokinetics, 35100, Izmir, Turkey.
SUMMARY. The aim of this study was to investigate cytotoxic activities, acute oral toxicity and gene mutagenicity in form of Salmonella/microsome mutagenicity assay (Ames) of imatinib microemulsion systems
(IM MEs). The MEs were prepared by the titration method using pseudo ternary phase diagram. For the
cytotoxicity tests, the hepatocellular cell lines Hep 3B (CRL-10741) and Hep G2 (HB-8064) were used. The
acute oral toxicity was assessed using the limit test in mice with a dose of 2000 mg/kg body weight. The
MEs consisted mainly of Labrasol/Capyrol 90/ Cremophor EL/ Cremophor EL-Span 80/Transcutol /water. In conclusion, no cytotoxic effects, no lethality during the acute oral toxicity test and no mutagenic potential in the TA98 nor in the TA100 strains could be observed on the here investigated cells. According to
the obtained results, the developed MEs could be a promising alternative to the available marketed oral
drug delivery.
RESUMEN. El objetivo de este estudio fue investigar las actividades citotóxicas, toxicidad oral aguda y mutagenicidad de genes utilizando el ensayo de mutagenicidad microsomal de Salmonella (Ames) en los sistemas de
microemulsión de imatinib (IM MEs). Los MEs fueron preparados por el método de titulación mediante diagrama de fases seudo ternario. Para los ensayos de citotoxicidad, se utilizaron las líneas de células hepatocelulares
Hep 3B (CRL-10741) y Hep G2 (HB-8064). La toxicidad oral aguda se evaluó mediante la prueba de límite en
ratones con una dosis de 2,000 mg/kg de peso corporal. Los MEs consistieron principalmente en Labrasol/ Capyrol 90/Cremophor EL/Cremophor EL-Span 80/Transcutol/agua. En conclusión, no hay efectos citotóxicos, ni letalidad durante la prueba de toxicidad oral aguda y potencial mutagénico en el TA98 ni en las cepas TA100 se
pudieron observar en las células aquí investigadas. De acuerdo con los resultados obtenidos, los MEs desarrollados podrían ser una alternativa prometedora a la administración oral de fármacos disponibles.
KEY WORDS: Ames test, cytotoxicity, hepatotoxicity, imatinib, microemulsion, oral toxicity.
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Author to whom correspondence should be addressed. E-mail: [email protected]; [email protected]
ISSN 0326 2383 (printed ed.)
ISSN 2362-3853 (on line ed.)