Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications

The purpose of this study was to develop a novel nanostructured lipid carrier (NLC) for the intravitreal-targeting delivery of triamcinolone acetonide (TA) by direct ocular instillation. A five-level central composite rotable design was used to study the influence of four different variables on the physicochemical characteristics of NLCs. The analysis of variance (ANOVA) statistical test was used to assess the optimization of NLC production parameters. The systems were produced by high pressure homogenization using Precirol (R) ATO5 and Squalene (R) as solid and liquid lipids respectively, and Lutrol (R) F68 as surfactant. Homogenization at 600 bar for 3 cycles of the optimized formulation resulted in the production of small NLC (mean diameter <200 nm) with a homogeneous particle size distribution (polydispersity index (PI) similar to 0.1), of negatively charged surface (similar to vertical bar 45 vertical bar mV) and high entrapment efficiency (similar to 95%). Surface morphology was assessed by SEM which revealed fairly spherical shape. DSC, WAXS and Fr-IR analyses confirmed that TA was mostly entrapped into the NLC, characterized by an amorphous matrix. In vivo Draize test showed no signs of ocular toxicity. (c) 2010 Elsevier B.V. All rights reserved.