title: 15d-PGJ2-Loaded Solid Lipid Nanoparticles: Physicochemical Characterization and Evaluation of Pharmacological Effects on Inflammation.
abstract: 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has physiological properties including pronounced anti-inflammatory activity, though it binds strongly to serum albumin. The use of solid lipid nanoparticles (SLN) can improve therapeutic properties increasing drug efficiency and availability. 15d-PGJ2-SLN was therefore developed and investigated in terms of its immunomodulatory potential. 15d-PGJ2-SLN and unloaded SLN were physicochemically characterized and experiments in vivo were performed. Animals were pretreated with 15d-PGJ2-SLN at concentrations of 3, 10 or 30 μg·kg-1 before inflammatory stimulus with carrageenan (Cg), lipopolysaccharide (LPS) or mBSA (immune response). Interleukins (IL-1β, IL-10 and IL-17) levels were also evaluated in exudates. The 15d-PGJ2-SLN system showed good colloidal parameters and encapsulation efficiency of 96%. The results showed that the formulation was stable for up to 120 days with low hemolytic effects. The 15d-PGJ2-SLN formulation was able to reduce neutrophil migration in three inflammation models tested using low concentrations of 15d-PGJ2. Additionally, 15d-PGJ2-SLN increased IL-10 levels and reduced IL-1β as well as IL-17 in peritoneal fluid. The new 15d-PGJ2-SLN formulation highlights perspectives of a potent anti-inflammatory system using low concentrations of 15d-PGJ2.
authors: Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Researcher Center, Campinas, Brazil.|Department of Environmental Engineering, São Paulo State University (UNESP), Sorocaba, Brazil.
authors: Nathalie Ferreira Silva
authors: NF
authors: de Melo
authors: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Campinas, Brazil.
authors: Cristina Gomes
authors: CG
authors: de Macedo
authors: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Campinas, Brazil.
authors: Ricardo
authors: R
authors: Bonfante
authors: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Campinas, Brazil.
authors: Henrique Ballassini
authors: HB
authors: Abdalla
authors: Department of Biochemistry, State University of Campinas (UNICAMP), Campinas, Brazil.
authors: Camila Morais Gonçalves
authors: CM
authors: da Silva
authors: Department of Biotechnology, University of Sorocaba (UNISO), Sorocaba, Brazil.
authors: Tatiane
authors: T
authors: Pasquoto
authors: Department of Biotechnology, University of Sorocaba (UNISO), Sorocaba, Brazil.
authors: Renata
authors: R
authors: de Lima
authors: Department of Environmental Engineering, São Paulo State University (UNESP), Sorocaba, Brazil.
authors: Leonardo Fernandes
authors: LF
authors: Fraceto
authors: Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Campinas, Brazil.
authors: Juliana Trindade
authors: JT
authors: Clemente-Napimoga
authors: Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Researcher Center, Campinas, Brazil.
authors: Marcelo Henrique
authors: MH
authors: Napimoga
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D041702:BALB 3T3 Cells; D002351:Carrageenan / Q000009:adverse effects; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007378:Interleukins / Q000235:genetics*; D008070:Lipopolysaccharides / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D020556:Neutrophil Infiltration / Q000187:drug effects*; D010316:Particle Size; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C477819:15-deoxyprostaglandin J2; D000893:Anti-Inflammatory Agents; D007378:Interleukins; D008070:Lipopolysaccharides; D002351:Carrageenan; D015230:Prostaglandin D2