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 ATO5 and squalene as solid and liquid lipids respectively, and Lutrol 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) approximately 0.1), of negatively charged surface (approximately |45| mV) and high entrapment efficiency (approximately 95%). Surface morphology was assessed by SEM which revealed fairly spherical shape. DSC, WAXS and FT-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.
Araújo
J
J
Department of Physical Chemistry, Institute of Nanoscience and Nanotechnology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
Gonzalez-Mira
E
E
Egea
M A
MA
Garcia
M L
ML
Souto
E B
EB
D000287:Administration, Topical; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004337:Drug Carriers; D004339:Drug Compounding; D005123:Eye / Q000098:blood supply* / Q000187:drug effects; D005989:Glycerides / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D015233:Models, Statistical; D049329:Nanostructures; D019308:Palmitic Acid / Q000737:chemistry; D010316:Particle Size; D011095:Polyethylenes / Q000737:chemistry; D011126:Polypropylenes / Q000737:chemistry; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013185:Squalene / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000737:chemistry*; D014961:X-Ray Diffraction
D020533:Angiogenesis Inhibitors; D004304:Dosage Forms; D004337:Drug Carriers; D005989:Glycerides; D008055:Lipids; D011095:Polyethylenes; D011126:Polypropylenes; D013229:Stearic Acids; D013501:Surface-Active Agents; D019308:Palmitic Acid; C031183:stearic acid; D013185:Squalene; C078661:UCON 50-HB-5100; D014222:Triamcinolone Acetonide