15d-PGJ(2)-Loaded Solid Lipid Nanoparticles: Physicochemical Characterization and Evaluation of Pharmacological Effects on Inflammation

Author(s)

Silva de Melo, Nathalie Ferreira ; de Macedo, Cristina Gomes ; Bonfante, Ricardo ; Abdalla, Henrique Ballassini ; Goncalves da Silva, Camila Morais ; Pasquoto, Tatiane ; de Lima, Renata ; Fraceto, Leonardo Fernandes ; Clemente-Napimoga, Juliana Trindade ; Napimoga, Marcelo Henrique

• Document type: Journal article
• Source: PLoS One; v. 11, n. 8 AUG 30 2016.
• Web of Science Citations: 2

Abstract

15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) 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-PGJ(2)-SLN was therefore developed and investigated in terms of its immunomodulatory potential. 15d-PGJ(2)-SLN and unloaded SLN were physicochemically characterized and experiments in vivo were performed. Animals were pretreated with 15d-PGJ(2)-SLN at concentrations of 3, 10 or 30 mu g.kg(-1) before inflammatory stimulus with carrageenan (Cg), lipopolysaccharide (LPS) or mBSA (immune response). Interleukins (IL-1 beta, IL-10 and IL-17) levels were also evaluated in exudates. The 15d-PGJ(2)-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-PGJ(2)-SLN formulation was able to reduce neutrophil migration in three inflammation models tested using low concentrations of 15d-PGJ(2). Additionally, 15d-PGJ(2)-SLN increased IL-10 levels and reduced IL-1 beta as well as IL-17 in peritoneal fluid. The new 15d-PGJ(2)-SLN formulation highlights perspectives of a potent anti-inflammatory system using low concentrations of 15d-PGJ(2). (AU)

• FAPESP's process: 14/11016-8 - Evaluation of immunopharmacologic effect of 15d-PGJ2 loaded solid lipid nanoparticles on inflammation
• Grantee: Nathalie Ferreira Silva de Melo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral