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 10 wt% of glyceryl behenate and 2.5 wt% of poloxamer 188. Immediately after production, Z-Ave of NiM-SLN was 166.1 ± 0.114 nm, with a polydispersity index (PI) of 0.171 ± 0051 and zeta potential nearly neutral (−3.10 ± 0.166 mV). A slight increase of Z-Ave was recorded for NiM-SLN stored at 25 °C for a period of 15 days, 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 24 h. Empty-SLN and NiM-SLN were nontoxic after exposing Caco-2 cells to the highest concentration (100 μg/mL) up to 48 hours (cell viability higher than 80%). NiM-SLN were lyophilized using different cryoprotectants, producing particles of 463.1 ± 36.63 nm (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.

Keywords:

• Nimesulide
• solid lipid nanoparticles
• physical stability
• factorial design experiment
• lyophilization
• trehalose
• cryoprotectants

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financed through the projects M-ERA-NET/0004/2015-PAIRED, receiving financial support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020. This work was also supported by the Spanish Ministry of Science and Innovation (MAT 2014–59134-R projects; 2014SGR-1023).