title: 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.
abstract: BACKGROUND
  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).
  
  
  METHODS
  NLCidispersions 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
  NLCishowed a Z-average below 200 nm, a highly positive zeta potential and an efficiency of encapsulation (EE) of ∼90%. The gelification of the NLCidispersion 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.
  
  
  CONCLUSIONS
  The strategy proposed in this work can be successfully used to increase the bioavailability and the therapeutic efficacy of conventional eyedrops.
authors.affiliation: a Laboratory of Pharmaceutical Technology, Department of Drug Sciences , Faculty of Pharmacy, Research Centre for Pharmaceutical Sciences, University of Porto , Porto , Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Almeida
authors.affiliation: a Laboratory of Pharmaceutical Technology, Department of Drug Sciences , Faculty of Pharmacy, Research Centre for Pharmaceutical Sciences, University of Porto , Porto , Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Lobão
authors.affiliation: b Department of Chemistry and Biochemistry , Faculty of Sciences, University of Porto , Porto , Portugal.|c Laboratori Derivati Organici , Milan , Italy , and.
authors.forename: Christian
authors.initials: C
authors.lastname: Frigerio
authors.affiliation: a Laboratory of Pharmaceutical Technology, Department of Drug Sciences , Faculty of Pharmacy, Research Centre for Pharmaceutical Sciences, University of Porto , Porto , Portugal.
authors.forename: Joel
authors.initials: J
authors.lastname: Fonseca
authors.affiliation: d UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences , Faculty of Pharmacy, University of Porto , Porto , Portugal.
authors.forename: Renata
authors.initials: R
authors.lastname: Silva
authors.affiliation: a Laboratory of Pharmaceutical Technology, Department of Drug Sciences , Faculty of Pharmacy, Research Centre for Pharmaceutical Sciences, University of Porto , Porto , Portugal.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Sousa Lobo
authors.affiliation: a Laboratory of Pharmaceutical Technology, Department of Drug Sciences , Faculty of Pharmacy, Research Centre for Pharmaceutical Sciences, University of Porto , Porto , Portugal.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Amaral
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000009:adverse effects / Q000737:chemistry*; D065346:Lubricant Eye Drops; D049329:Nanostructures / Q000009:adverse effects / Q000737:chemistry*; D009883:Ophthalmic Solutions; D020442:Poloxamer / Q000009:adverse effects / Q000737:chemistry*; D012212:Rheology; D013499:Surface Properties; D014783:Viscosity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D065346:Lubricant Eye Drops; D009883:Ophthalmic Solutions; D020442:Poloxamer; D007052:Ibuprofen
keywords: Colloidal dispersions; in situ gelling systems; lipid nanoparticles; ophthalmic; poloxamers