Preparation, characterization and biocompatibility studies of thermoresponsive eyedrops based on the combination of nanostructured lipid carriers (NLC) and the polymer Pluronic F-127 for controlled delivery of ibuprofen

摘要

Abstract Context: Nanostructured lipid carrier (NLC) dispersions present low viscosity and poor mucoadhesive properties, which reduce the pre-corneal residence time and consequently, the bioavailability of ocular drugs. Objective: The aim of this study was to prepare thermoresponsive eyedrops based on the combination of lipid nanoparticles and a thermoresponsive polymer with mucomimetic properties (Pluronic? F-127). Materials and methods: NLQ dispersions were prepared based on the melt-emulsification and ultrasonication technique. Physicochemical and morphological characteristics of the colloidal dispersions were evaluated. The formulation was also investigated for potential cytotoxicity in Y-79 human retinoblastoma cells and the in vitro drug release profile of the ibuprofen was determined. Results: NLQ showed a Z-average below 200 nm, a highly positive zeta potential and an efficiency of encapsulation (EE) of ~90%. The gelification of the NLQ dispersion with 15% (w/w) Pluronic? F-127 did not cause significant changes to the physicochemical properties. The potential NLC-induced cytotoxicity was evaluated by the Alamar Blue reduction assay in Y-79 cells, and no relevant cytotoxicity was observed after exposure to 0-100ng/mL NLC for up to 72 hours. The optimized formulations showed a sustained release of ibuprofen over several hours. Discussion and conclusion: The strategy proposed in this work can be successfully used to increase the bioavailability and the therapeutic efficacy of conventional eyedrops.