Optimization of nimesulide-loaded solid lipid nanoparticles (SLN) by factorial design, release profile and cytotoxicity in human Colon adenocarcinoma cell line

Abstract

The aim of this work is development of a nontoxic, long-term stable solid lipid nanoparticles (SLN) formulation for the loading of Nimesulide (NiM) by a 22 factorial design. The optimized formulation was composed of 10wt% of glyceryl behenate and 2.5wt% of poloxamer 188. Immediately after production, Z-Ave of NiM-SLN was 166.1±0.114nm, with a polydispersity index (PI) of 0.171±0051 and zeta potential nearly neutral (3.10±0.166mV). A slight increase of Z-Ave was recorded for NiM-SLN stored at 25°C for a period of 15days, whereas at 4°C particles kept size within similar range. Long-term stability was monitored using TurbiscanLab®, showing a high stability of the nanoparticles with variations in the backscattering profiles below 10%. The release profile of NiM-SLN followed a sustained pattern with ca. 30% of drug released up to 24h. Empty-SLN and NiM-SLN were nontoxic after exposing Caco-2 cells to the highest concentration (100g/mL) up to 48hours (cell viability higher than 80%). NiM-SLN were lyophilized using different cryoprotectants, producing particles of 463.1±36.63nm (PI 0.491±0.027) with 5% trehalose. Solid character of NiM-SLN was confirmed by DSC, recording a recrystallization index of 83% for NiM-SLN and of 74% for lyophilized SLN.