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

Pharm Dev Technol. 2017 May;22(3):336-349. doi: 10.3109/10837450.2015.1125922. Epub 2015 Dec 20.

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: NLCi 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: NLCi showed a Z-average below 200 nm, a highly positive zeta potential and an efficiency of encapsulation (EE) of ∼90%. The gelification of the NLCi 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 0-100 µg/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.

Keywords: Colloidal dispersions; in situ gelling systems; lipid nanoparticles; ophthalmic; poloxamers.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Delayed-Action Preparations
  • Drug Carriers / adverse effects
  • Drug Carriers / chemistry*
  • Drug Compounding / methods*
  • Drug Liberation
  • Drug Stability
  • Humans
  • Ibuprofen / administration & dosage*
  • Ibuprofen / adverse effects
  • Lipids / adverse effects
  • Lipids / chemistry*
  • Lubricant Eye Drops
  • Nanostructures / adverse effects
  • Nanostructures / chemistry*
  • Ophthalmic Solutions
  • Poloxamer / adverse effects
  • Poloxamer / chemistry*
  • Rheology
  • Surface Properties
  • Viscosity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Delayed-Action Preparations
  • Drug Carriers
  • Lipids
  • Lubricant Eye Drops
  • Ophthalmic Solutions
  • Poloxamer
  • Ibuprofen