title: The effect of sucrose esters on a culture model of the nasal barrier.
abstract: Sucrose esters are effective solubilizers and there is an interest to use them as pharmaceutical excipients for nasal drug delivery. We have determined for the first time the non-toxic doses of laurate and myristate sucrose esters by four independent methods, and their effects on epithelial permeability using RPMI 2650 human nasal epithelial cell line. Based on real-time cell electronic sensing, MTT dye conversion and lactate dehydrogenase release methods reference surfactant Cremophor RH40 proved to be the least toxic excipient, and could be used at 5mg/mL concentration for 1h in epithelial cells without cellular damage. The non-toxic dose of Tween 80 was 1 mg/mL, while the dose of laurate and myristate sucrose esters that could be safely used on cells for 1 h was 0.1 mg/mL. Both the reference surfactants and the sucrose esters significantly enhanced the permeability of epithelial cell layers for the paracellular marker FITC-labelled 4.4 kDa dextran at 0.1 mg/mL concentration. The effects of sucrose esters on epithelial permeability were dose-dependent. These data indicate that laurate and myristate sucrose esters can be potentially used as permeability enhancers in nasal formulations to augment drug delivery to the systemic circulation.
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári Krt. 62, H-6726 Szeged, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Kürti
authors.forename: Szilvia
authors.initials: S
authors.lastname: Veszelka
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bocsik
authors.forename: Ngo Thi Khue
authors.initials: NT
authors.lastname: Dung
authors.forename: Béla
authors.initials: B
authors.lastname: Ozsvári
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
authors.forename: Agnes
authors.initials: A
authors.lastname: Kittel
authors.forename: Piroska
authors.initials: P
authors.lastname: Szabó-Révész
authors.forename: Mária A
authors.initials: MA
authors.lastname: Deli
mesh_terms: D002460:Cell Line; D003911:Dextrans / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005079:Excipients / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D010539:Permeability; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000633:toxicity; D011136:Polysorbates / Q000494:pharmacology / Q000633:toxicity; D013395:Sucrose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D003911:Dextrans; D005079:Excipients; D011136:Polysorbates; C015219:fluorescein isothiocyanate dextran; C018152:sucrose monolaurate; C022131:cremophor; D011092:Polyethylene Glycols; D013395:Sucrose; C068214:sucrose myristate; D007770:L-Lactate Dehydrogenase; D016650:Fluorescein-5-isothiocyanate