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.

Bondì, M.L., Craparo, E.F., Picone, P., Giammona, G., Di Gesù, R., & Di Carlo, M. (2013). LIPID NANOCARRIERS CONTAINING ESTER PRODRUGS OF FLURBIPROFEN. PREPARATION, PHYSICAL-CHEMICAL CHARACTERIZATION AND BIOLOGICAL STUDIES. JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, 9(2), 238-246.

LIPID NANOCARRIERS CONTAINING ESTER PRODRUGS OF FLURBIPROFEN. PREPARATION, PHYSICAL-CHEMICAL CHARACTERIZATION AND BIOLOGICAL STUDIES

CRAPARO, Emanuela Fabiola;GIAMMONA, Gaetano;Di Gesu', Roberto;
2013

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.
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
Bondì, M.L., Craparo, E.F., Picone, P., Giammona, G., Di Gesù, R., & Di Carlo, M. (2013). LIPID NANOCARRIERS CONTAINING ESTER PRODRUGS OF FLURBIPROFEN. PREPARATION, PHYSICAL-CHEMICAL CHARACTERIZATION AND BIOLOGICAL STUDIES. JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, 9(2), 238-246.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/93474
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