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.

Potential of mucoadhesive nanocapsules in drug release and toxicology in zebrafish

“…Through mathematical fitting, it was possible to compare the two release curves, and the constant values (k) demonstrated that BENZ is released faster from NPMAs than NPs due to the presence of chitosan coating, which probably translocates BENZ molecules from the surface. The values of r indicated the main mechanism involved in the release of the drug was Fickian diffusion, as also found previously for other polymeric nanoparticles containing articaine [24,25] and solid lipid nanoparticles containing prostaglandin J 2 [27] .…”

“…Mathematical modeling was employed to elucidate the drug release from the nanoparticle systems. The Baker-Lonsdale model has been used previously by our group to evaluate the results of release curves involving nanoparticles [ 24 , 25 , 27 ]. Linear regression showed correlation coefficient ( r ) values of 0.978 and 0.988, and release constant ( k ) values of 4.24822 x 10 −5 (± 2.83661 x 10 −6 ) min -1 and 6.65378x 10 −5 (± 4.27674 x 10 −6 ) min -1 , for NPs and NPMAs, respectively.…”

“…The experiment was carried out in triplicate and BENZ concentration was determined by HPLC. The drug release mechanism was also evaluated using the Baker-Lonsdale theoretical model, which is based on Fickian diffusion to elucidate drug release from spherical systems [ 24 , 27 ].…”

“…The videos of Brownian motion were analyzed with the NanoSight 2.3 software. Each replicate consisted of five measurements of about 2,000 particles counted in each analysis [26,27].…”

15d-PGJ2-loaded nanocapsules ameliorate experimental gout arthritis by reducing pain and inflammation in a PPAR-gamma-sensitive manner in mice

“…Nanocapsules consist of polymeric involucres around a nucleus generally oily used to prolong pharmacological activity and decrease toxicity of molecules 20 . 15d-PGJ 2 was shown to be released slowly from nanocapsules, which avoided inactivation or reduction of its biological activity 21 , 22 by reactions that could include Michael’s addition 23 . Another possibility is that cells could uptake nanoparticles loaded with 15d-PGJ 2 resulting in enhanced 15d-PGJ 2 levels inside the cells as well as increased pharmacological response.…”