title: Studies on the formation of polymeric nano-emulsions obtained via low-energy emulsification and their use as templates for drug delivery nanoparticle dispersions.
abstract: Ethylcellulose nanoparticles have been obtained from O/W nano-emulsions of the water/polyoxyethylene 10 oleyl ether/[ethyl acetate+4wt% ethylcellulose] system by low energy-energy emulsification at 25°C. Nano-emulsions with droplet sizes below 200nm and high kinetic stability were chosen for solubilising dexamethasone (DXM). Phase behaviour, conductivity and optical analysis studies of the system have evidenced for the first time that both, the polymer and the drug play a role on the structure of the aggregates formed along the emulsification path. Nano-emulsion formation may take place by both, phase inversion and self-emulsification. Spherical polymeric nanoparticles containing surfactant, showing sizes below 160nm have been obtained from the nano-emulsions by organic solvent evaporation. DXM loading in the nanoparticles was high (>90%). The release kinetics of nanoparticle dispersions with similar particle size and encapsulated DXM but different polymer to surfactant ratio were studied and compared to an aqueous DXM solution. Drug release from the nanoparticle dispersions was slower than from the aqueous solution. While the DXM solution showed a Fickian release pattern, the release behaviour from the nanoparticle dispersions was faster than that expected from a pure Fickian release. A coupled diffusion/relaxation model fitted the results very well, suggesting that polymer chains undergo conformational changes enhancing drug release. The contribution of diffusion and relaxation to drug transport in the nanoparticle dispersions depended on their composition and release time. Surfactant micelles present in the nanoparticle dispersion may exert a mild reservoir effect. The small particle size and the prolonged DXM release provided by the ethylcellulose nanoparticle dispersions make them suitable vehicles for controlled drug delivery applications.
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) and CIBER de Bioingeniería, Biomateriales y Nanomedicina (BBN), Jordi Girona, 18-26, 08034 Barcelona, Spain. Electronic address: gabriela.caldero@gmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Calderó
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) and CIBER de Bioingeniería, Biomateriales y Nanomedicina (BBN), Jordi Girona, 18-26, 08034 Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Montes
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) and CIBER de Bioingeniería, Biomateriales y Nanomedicina (BBN), Jordi Girona, 18-26, 08034 Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Llinàs
authors.affiliation: Departament de Farmàcia i Tecnologia Farmacèutica, Univ. de Barcelona, Unitat Associada d'I +D al CSIC- Av Joan XXIII, s/n, 08028 Barcelona, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: García-Celma
authors.affiliation: Departament d'Enginyeria Química, Univ. de Barcelona, C/Martí i Franquès 1, 08028 Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Porras
authors.affiliation: Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) and CIBER de Bioingeniería, Biomateriales y Nanomedicina (BBN), Jordi Girona, 18-26, 08034 Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Solans
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D004655:Emulsions; D011108:Polymers
keywords: DXM release; Low-energy emulsification; Nano-emulsion; Nanoparticle dispersion; PIC method; Self-emulsification