SIMVASTATIN-LOADED NANOCAPSULES REDUCE TNF-Α EXPRESSION IN RAT PERITONEUM AFTER INFUSION OF PERITONEAL DIALYSIS SOLUTION

Abstract

Objective: Obteinment and characterizing polymeric nanocapsules of simvastatin (SV), and investigating their action in an experimental model of peritoneal fibrosis induced in a rat by the infusion of peritoneal dialysis (PD) solution.

Methods: Poly (ε-caprolactone) nanocapsules containing SV (NC-SV) were prepared by interfacial deposition of a preformed polymer. A suspension of nanoparticles with no drug was prepared as negative control. The average particle size and polydispersity index were measured by photon correlation spectroscopy. The morphological and surface evaluation of prepared nanocapsules was performed using field emission scanning electron microscopy. The ultra-high performance liquid chromatography with photodiode array detection method was used to evaluate the drug encapsulation efficiency. The release profiles of SV from polymeric nanocapsules were obtained by dialysis diffusion technique. The Animal Study was performed in a total of 48 male Wistar rats (Rattus norvegicus) divided in four groups: Sham, PD group, SV group, and Simvastatin-loaded nanocapsules group (NC-SV). After 28 days, tissue samples were surgically removed from the abdominal to perform histological and immunohistochemistry analysis. The statistical analysis was performed by one-way ANOVA followed by Bonferroni test, or by Kruskal–Wallis.

Results: NC-SV presented suitable particle parameters with a mean particle size of 332 nm, and an encapsulation efficiency of 99.87±0.46%. The expression of tumor necrosis factor-alpha (TNF-α) was significantly different in NC-SV group.

Conclusion: SV-loaded nanocapsules for controlled drug delivery were suitably prepared. This nanoformulation remarkable decreased the TNF-α tissue expression even at low SV dose in a chronic PD model.