Preparation and characterization of GOFA-loaded lipid nanoparticles.

To prepare and characterize lipid nanoparticles loaded with GOFA [3-(4’-geranyloxy-3’-methoxyphenyl)-2-trans propenoic acid], a natural anti-inflammatory agent, in order to overcome its solubility issues. Methods. GOFA was produced by one-pot, two-step synthesis. Briefly, the methyl ester of ferulic acid was treated, first, with geranyl bromide and K2CO3 and, then, with a basic medium to obtain the final product. Lipid nanoparticles (Solid lipid nanoparticles, SLN and nanostructured lipid carriers, NLC) were prepared using the solvent injection method. Briefly, 100 mg of the chosen lipid mixture were dissolved in 5 ml of acetone and injected by a syringe in 50 ml of distilled water containing 1% (w/v) of pluronic®F68 under high speed stirring (60°C, 8000rpm). Cetylpalmitate, softisan®142 and softisan®154 were used, alone o in combination with cetyl alcohol, as lipid matrix. For the preparation of NLC, mygliol or oleic acid were used as oil phase. In order to investigate the influence of the preparation method on particle characteristics, the optimized formulation was produced using the high pressure homogenization technique as well (65°C, 7 cycles at 150000 KPa). Results. GOFA was obtained with a overall yield of 98%. The best blank SLN formulations were obtained with cetilpalmitate or softisan®154, with or without 33% (w/w) of cetyl alcohol, and the nanoparticle mean diameters were 270, 525, 296, 275 nm, respectively. The best blank NLC were obtained using softisan®154:cetyl alcohol (2:1) or softisan®154 as solid matrix and 20% (w/w) of mygliol® (238 and 253 nm, respectively). Softisan®154-cetyl alcohol (2:1) with 30% (w/w) of oleic acid produced particles with the smallest size (205 nm). The formulations showed a good physical stability when stored at 4°C. GOFA was successfully loaded within Softisan®154-cetyl alcohol-oleic acid NLC with a actual drug content of about 4% (w/w) and a mean diameter of about 280 nm. The high pressure homogenization technique produced smaller particles (≈187 nm). Conclusion. GOFA was successfully formulated within lipid nanoparticles having suitable dimensions for both parenteral administration and intracellular targeting.