title: Lipid nanocarriers containing ester prodrugs of flurbiprofen preparation, physical-chemical characterization and biological studies.
abstract: In this paper, the preparation, chemical-physical, technological and in vitro characterization of nanostructured lipid carriers (NLC) carrying R-flurbiprofen ester prodrugs, were analyzed for a potential pharmaceutical application. R-flurbiprofen was chosen as a model drug because it has been found to play an effective role in counteracting secretases involved in neurodegenerative diseases, although it does not cross the Blood Brain Barrier (BBB). In this study, two R-flurbiprofen ester prodrugs (ethyl and hexyl) were successfully synthesized and entrapped into non-pegylated and pegylated NLC. The obtained systems showed average diameters in the colloidal size range, negative zeta potential values and a good loading capacity. Drug release studies in physiological media on all drug-loaded samples showed a controlled drug release both at at pH 7.4 (containing esterase or not) and in human plasma of each ester prodrug, with a complete hydrolysis to R-flurbiprofen in media containing esterase. Empty and ethyl prodrug-loaded NLC were also demonstrated to have no cytotoxicity on human neuroblastoma (LAN5) cells, while hexyl prodrug-loaded NLC caused a reduction of cell viability probably due to a better capability of prodrug-loaded NLC to cross the cell membrane than the free compounds. These data were confirmed by microscopical observation, in which only the cells treated with hexyl prodrug-loaded NLC showed morphological changes. Outcoming data suggest that NLC could be potential carriers for parenteral administration of ethyl ester of R-flurbiprofen in the treatment of neurodegenerative diseases such as Alzheimer's.
authors.affiliation: Istituto per Io Studio dei Materiali Nanostrutturati (ISMN) U.O.S. Palermo, CNR, via Ugo La Malfa, 153, 90146 Palermo, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Bondìl
authors.forename: E F
authors.initials: EF
authors.lastname: Craparo
authors.forename: P
authors.initials: P
authors.lastname: Picone
authors.forename: G
authors.initials: G
authors.lastname: Giammona
authors.forename: R
authors.initials: R
authors.lastname: Di Gesù
authors.forename: M
authors.initials: M
authors.lastname: Di Carlo
mesh_terms: D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry*; D005480:Flurbiprofen / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D049329:Nanostructures; D010316:Particle Size; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D055672:Static Electricity
chemical_list: D004337:Drug Carriers; D004952:Esters; D008055:Lipids; D011355:Prodrugs; D005480:Flurbiprofen