Optimization of nanostructured lipid carriers loaded with retinoids by central composite design

The aim of this study was to design and optimize a new formulation of lipid nanoparticles for the topical administration of retinoids. The standard procedure involves nanostructured lipid carriers (NLCs) synthesized by the miniemulsion methodology, using sunflower oil as a bioactive ingredient and retinyl palmitate (RP) as model retinoid. A 5-factor, 3-level central composite design was used to predict responses and construct 3D-response contour plots. The independent variables were the concentration of total lipids, solid lipid, surfactant, encapsulated retinoid and number of carbons on the solid lipid fatty acid chain length, in function of the selected responses as the particle size, surface charge of the nanoparticles and the encapsulation efficiency (EE %) at 3 levels. Experimental trials were performed at all 31 possible combinations. An optimized NLC composition of 2.5% total lipids, 2.0% myristic acid and 0.5% sunflower oil and 1.5% of surfactant Tween 80 was reached. The type of surfactant was adjusted from Tween 80 to Span 80 to improve the electrostatic stability of the lipid nanoparticles and the resultant optimized NLC formulation was evaluated to incorporate another two retinoids as tretinoin (TRT) and adapalene (ADP). The resultant retinoid delivery systems were characterized in terms of particle size and electrostatic stability, morphology, crystallinity of the lipid matrix, EE (%) and drug loading capacity and release profile. Particle sizes of 134.5 +/- 5.4 nm and zeta potential values of -57.0 +/- 2.8 mV were obtained for optimized ADP-NLCs and high entrapment efficiency values were obtained for RP-NLC, TRT-NLC and ADP-NLC as 84.4 +/- 3.0%, 84.1 +/- 7.8% and 73.7 +/- 3.3%, respectively. DSC analysis indicated that the melting temperatures of the three optimized NLCs loaded with the retinoids were above 40 degrees C, proving to be suitable for use in topical administration. The in vitro drug release studies were conducted for 48 h, using a dialysis regenerated cellulose membrane. The results demonstrated a very well-controlled release of RP and TRT, which improves the stability of these active compounds and confirms a high encapsulation efficiency. (C) 2019 Elsevier B.V. All rights reserved.