title: Controlled release of methotrexate from w/o microemulsion and its in vitro antitumor activity.
abstract: The objective of this study was to prepare the microemulsion of methotrexate (M-MTX) for oral use and to investigate the suppressive effect of MTX-loaded microemulsion on MCF-7 human breast cancer cells. At the same time this effect of M-MTX was compared with those of a solution of the drug (Sol-MTX). Microemulsion was composed of soybean oil as oil phase, a mixture of Cremophore EL and Span 80 as surfactants, and isopropyl alcohol as co-surfactant, and 0.2 N NaOH as the aqueous phase. MTX was added into microemulsion at the last stage. We clearly demonstrated that M-MTX had a significant cytotoxic effect on breast cancer cell lines and the cytotoxic effect of M-MTX was significantly more than that of solutions (p < 0.05) and IC(50) value for M-MTX was 40 ng/mL. We also examined M-MTX and Sol-MTX on a model biological environmental model. For this purpose a gastrointestinal cell culture model, the Caco-2 cell line, was used to investigate the cytotoxic effects of the polymeric carrier and its effect on the cell monolayer integrity. The differences between the viability of cells for M-MTX and Sol-MTX were significantly different when applied to ANOVA according to 2 x 8 factorial randomized design (p:0.016; for alpha: 0.05, power : 0.695). According to the in vitro cytotoxicity studies, we concluded that when MTX was incorporated into the microemulsion (M-MTX), which is a new drug carrier system, it suppresses tumour cell growth on multiple tumor lines. These results indicate that M-MTX may exert a low cytotoxic effect on normal cells and may be effective as an antitumor agent that induces apoptosis.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ege, Izmir, Turkey. yesim.karasulu@ege.edu.tr
authors.forename: H Yesim
authors.initials: HY
authors.lastname: Karasulu
authors.forename: Bülent
authors.initials: B
authors.lastname: Karabulut
authors.forename: Erdem
authors.initials: E
authors.lastname: Göker
authors.forename: Tamer
authors.initials: T
authors.lastname: Güneri
authors.forename: Franz
authors.initials: F
authors.lastname: Gabor
mesh_terms: D019840:2-Propanol / Q000737:chemistry; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001943:Breast Neoplasms / Q000473:pathology; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004655:Emulsions; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006601:Hexoses / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D012972:Sodium Hydroxide / Q000737:chemistry* / Q000633:toxicity; D012995:Solubility; D013024:Soybean Oil / Q000737:chemistry* / Q000633:toxicity; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D006601:Hexoses; D013501:Surface-Active Agents; C018665:sorbitan monooleate; D012972:Sodium Hydroxide; C000515:cremophor EL; D013024:Soybean Oil; D019840:2-Propanol; D005990:Glycerol; D008727:Methotrexate