MAGNETIC NANOCARRIERS FOR THE CONTROLLED RELEASE OF DICLOFENAC

MARIELA AGOTEGARAY; SANTIAGO PALMA; VERÓNICA LASSALLE

Encuentro; II Reunión Internacional de Ciencias Farmaceúticas; 2012

Introduction Magnetic nanoparticles(MNPs) find active applications in biomedical field, for example, as targeted drug delivery systems. Their development is suitable for transporting a specific drug directly to the site of disease avoiding adverse effects over different parts of the body(1). We have developed a novel device consisting in iron oxide [magnetite(MG), Fe3O4] MNPs coated with oleic acid(OA) and chitosan(CS) for the delivery of the anti-inflammatory drug Diclofenac. A study of the in vitro release of the drug has been performed. 3O4] MNPs coated with oleic acid(OA) and chitosan(CS) for the delivery of the anti-inflammatory drug Diclofenac. A study of the in vitro release of the drug has been performed. Materials and methods MNPs containing MG and OA were prepared following the co-precipitation method (2). Incorporation of CS was conducted by nanoprecipitation: MG/OA MNPs were dispersed in acetone; after sonication, a chitosan-acetic acid solution was added. The resulting precipitate was separated with a high-power Nd magnet, washed with water and dried. Diclofenac(Dic) (5 mg mL-1) loading onto the MNPs was achieved by physical adsorption in phosphate buffer(PBS) pH 7.4 leading MG/OA/CS-Dic. The dispersion was incubated at room temperature under stirring for 24 hours. Samples were withdrawn at different intervals of time to determine drug incorporation by UV absorption at 276nm. Nanocarriers were characterized by Dynamic Light Scattering (DLS) at 25ºC using distilled water, acetone and N,N´-dimethylformamide as dispersants, zeta potential measurements, FTIR-DRIFTS spectroscopy and transmission electronic microscopy(TEM). The Diclofenac release study was performed in vitro using PBS(pH 7.4) as release medium. A dispersion containing MG/AO/CS-Dic particles was incubated at 37ºC under magnetic stirring. Samples of the supernatant were withdrawn at prefixed times to analyze drug content by UV/Visible spectroscopy. The release data was fitted with available mathematical models aiming to determine the kinetic and mechanism of release. Nanocarriers were characterized by Dynamic Light Scattering (DLS) at 25ºC using distilled water, acetone and N,N´-dimethylformamide as dispersants, zeta potential measurements, FTIR-DRIFTS spectroscopy and transmission electronic microscopy(TEM). The Diclofenac release study was performed in vitro using PBS(pH 7.4) as release medium. A dispersion containing MG/AO/CS-Dic particles was incubated at 37ºC under magnetic stirring. Samples of the supernatant were withdrawn at prefixed times to analyze drug content by UV/Visible spectroscopy. The release data was fitted with available mathematical models aiming to determine the kinetic and mechanism of release. -1) loading onto the MNPs was achieved by physical adsorption in phosphate buffer(PBS) pH 7.4 leading MG/OA/CS-Dic. The dispersion was incubated at room temperature under stirring for 24 hours. Samples were withdrawn at different intervals of time to determine drug incorporation by UV absorption at 276nm. Nanocarriers were characterized by Dynamic Light Scattering (DLS) at 25ºC using distilled water, acetone and N,N´-dimethylformamide as dispersants, zeta potential measurements, FTIR-DRIFTS spectroscopy and transmission electronic microscopy(TEM). The Diclofenac release study was performed in vitro using PBS(pH 7.4) as release medium. A dispersion containing MG/AO/CS-Dic particles was incubated at 37ºC under magnetic stirring. Samples of the supernatant were withdrawn at prefixed times to analyze drug content by UV/Visible spectroscopy. The release data was fitted with available mathematical models aiming to determine the kinetic and mechanism of release. in vitro using PBS(pH 7.4) as release medium. A dispersion containing MG/AO/CS-Dic particles was incubated at 37ºC under magnetic stirring. Samples of the supernatant were withdrawn at prefixed times to analyze drug content by UV/Visible spectroscopy. The release data was fitted with available mathematical models aiming to determine the kinetic and mechanism of release. Results and discussion Analysis by FTIR-DRIFTS of MG/OA/CS and MG/OA/CS-Dic confirm the incorporation of Diclofenac to MNPs. The maximum quantity of Diclofenac adsorbed was detected at the fifth hour of the assay. Drug encapsulation efficiency was estimated in 54% and Diclofenac loading was 29%. These results are satisfactory in comparison with other MNPs loaded with the same drug using the same incorporation method(3). From DLS measurements data(Table 1), MG/OA/CS-Dic presents polidispersity indexes between 0.01 and 0.5(4), being monodispersed in the solvents studied. This aspect results crucial for in vivo application of this system since the route of administration of a medicament depends on this parameter. In general, particles less than 5μ size can be used for intravenous route(5). By this way, these MNPs loaded with Diclofenac could be suitable for intravenous injection for the potential treatment of localized inflammatory diseases. Zeta potential measurement results indicate that no ionic interaction occurs between Diclofenac and MNPs. TEM micrographies show spherical and homogeneous shape particles. in vivo application of this system since the route of administration of a medicament depends on this parameter. In general, particles less than 5μ size can be used for intravenous route(5). By this way, these MNPs loaded with Diclofenac could be suitable for intravenous injection for the potential treatment of localized inflammatory diseases. Zeta potential measurement results indicate that no ionic interaction occurs between Diclofenac and MNPs. TEM micrographies show spherical and homogeneous shape particles. Table 1. Average diameter of MG/OA/CS-Dic/polydispersity index. Water Acetone Dmf 368nm/0.389 169nm/0.349 324nm/0.254