title: Development and characterization of anti-inflammatory activity of curcumin-loaded biodegradable microspheres with potential use in intestinal inflammatory disorders.
abstract: This research addresses the development and in vitro evaluation of a microparticulate system intended for intestine-targeted delivery of curcumin (CRM), a natural polyphenol with anti-inflammatory properties. Microspheres (Ms) based on zein (ZN) and Gantrez®AN119 (PVMMA) were prepared by spray-drying and coated with a pH-sensitive polymer (Eudragit®FS30D). An experimental design was performed to optimize the microparticulate formulation. A detailed characterization of systems was carried out by SEM, DSC, FTIR, particle size, ζ potential measurements and in vitro CRM release. The optimized formulation was evaluated in LPS-stimulated RAW 264.7 macrophages to investigate its anti-inflammatory activity. FTIR and DSC studies suggest a predominant presence of α-helix structure for ZN when formulated and also, a strong interaction between components. The stabilization of α-helix by PVMMA or CRM would take place by hydrogen bonds. Although the encapsulation efficiency was high (89%) for ZN/PVMMA Ms, the coating process with Eudragit®led to an EE decrease of 62%. Coating of Ms was found to retain a 20% of drug within 6h of release, although a strong initial burst release was observed. Cells viability and apoptosis were not affected when cells were co-incubated with coated Ms with CRM. The exposure of unstimulated cells to Ms did not show any effect on NO and PGE2production. However, a reduction in NO and PGE2production was obtained when CRM-loaded Ms were co-incubated with stimulated macrophages. Further, this inhibition was significantly higher compared to the decrease obtained when Ms with pure CRM were used in culture, which suggested a synergistic effect of CRM and Ms. Finally, CRM-loaded Ms caused a significant inhibition of analysed pro-inflammatory cytokines (TNFα, IL-1β, NOS2, COX-2) in macrophages stimulated with LPS. All these results confirm the advantageous features of ZN/PVMMA microspheres as a serious alternative for delivering CRM to reduce the inflammatory activity at intestinal regions affected by inflammatory bowel diseases.
authors.affiliation: Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Blanco-García
authors.affiliation: Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Otero-Espinar
authors.affiliation: Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Blanco-Méndez
authors.affiliation: Departamento de Microbiología y Parasitología, Instituto de Investigación y Análisis Alimentarios, Universidad de Santiago de Compostela, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Leiro-Vidal
authors.affiliation: Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Spain. Electronic address: asteriam.luzardo@usc.es.
authors.forename: A
authors.initials: A
authors.lastname: Luzardo-Álvarez
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D065546:Drug Liberation; D015212:Inflammatory Bowel Diseases; D008070:Lipopolysaccharides; D008298:Maleates / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009569:Nitric Oxide / Q000378:metabolism; D011109:Polymethacrylic Acids / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D000067996:RAW 264.7 Cells; D015028:Zein / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D008298:Maleates; D011109:Polymethacrylic Acids; D011145:Polyvinyls; C058026:polyvinylmethoxyethylene-maleic anhydride copolymer; C038300:methylmethacrylate-methacrylic acid copolymer; D009569:Nitric Oxide; D015028:Zein; D003474:Curcumin; D015232:Dinoprostone
keywords: Inflammatory cell response; Intestinal delivery; Microspheres; PVMMA; Zein