title: Cytotoxicity of Different Excipients on RPMI 2650 Human Nasal Epithelial Cells.
abstract: The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need to be tested in appropriate models for toxicity. The aim of the study was to measure the cytotoxicity of six pharmaceutical excipients, which could help to reach larger residence time, better permeability, and increased solubility dissolution rate. The following excipients were investigated on RPMI 2650 human nasal septum tumor epithelial cells: β-d-mannitol, sodium hyaluronate, α and β-cyclodextrin, polyvinyl alcohol and methylcellulose. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye conversion assay and real-time impedance analysis were used to investigate cytotoxicity. No excipient showed toxicity at 0.3% (w/v) concentration or below while 1% concentration a significantly reduced metabolic activity was measured by MTT assay for methylcellulose and cyclodextrins. Using impedance measurements, only β-cyclodextrin (1%) was toxic to cells. Mannitol at 1% concentration had a barrier opening effect on epithelial cells, but caused no cellular damage. Based on the results, all additives at 0.3%, sodium hyaluronate and polyvinyl alcohol at 1% concentrations can be safely used for nasal formulations.
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary. horvath.tamas@pharm.u-szeged.hu.|Goodwill Pharma Ltd., Cserzy Mihály u. 32, Szeged H-6724, Hungary. horvath.tamas@pharm.u-szeged.hu.
authors.forename: Tamás
authors.initials: T
authors.lastname: Horváth
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary. bartoscsilla@pharm.u-szeged.hu.
authors.forename: Csilla
authors.initials: C
authors.lastname: Bartos
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary. bocsik@brc.hu.|Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári körút 62, Szeged H-6726, Hungary. bocsik@brc.hu.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bocsik
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary. kisslori@gmail.com.|Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári körút 62, Szeged H-6726, Hungary. kisslori@gmail.com.
authors.forename: Lóránd
authors.initials: L
authors.lastname: Kiss
authors.affiliation: Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári körút 62, Szeged H-6726, Hungary. veszelka.szilvia@brc.mta.hu.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Veszelka
authors.affiliation: Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári körút 62, Szeged H-6726, Hungary. deli.maria@brc.mta.hu.
authors.forename: Mária A
authors.initials: MA
authors.lastname: Deli
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary. rita-techno@freemail.hu.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Újhelyi
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary. revesz@pharm.u-szeged.hu.
authors.forename: Piroska
authors.initials: P
authors.lastname: Szabó-Révész
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary. arita@pharm.u-szeged.hu.
authors.forename: Rita
authors.initials: R
authors.lastname: Ambrus
mesh_terms: D045744:Cell Line, Tumor; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000627:therapeutic use; D008353:Mannitol / Q000737:chemistry / Q000627:therapeutic use; D008747:Methylcellulose / Q000737:chemistry; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D009300:Nasal Septum / Q000187:drug effects* / Q000473:pathology; D009669:Nose Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011142:Polyvinyl Alcohol / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D008353:Mannitol; D011142:Polyvinyl Alcohol; D006820:Hyaluronic Acid; D008747:Methylcellulose
keywords: MTT dye assay; cytotoxicity; nasal; nasal formulation; real-time impedance analysis