title: Thermosensitive in situ nanogel as ophthalmic delivery system of curcumin: development, characterization, in vitro permeation and in vivo pharmacokinetic studies.
abstract: BACKGROUND
  The nanogel combining cationic nanostructured lipid carriers (CNLC) and thermosensitive gelling agent could enhance preocular retention and ocular permeation capacity of curcumin (CUR).
  
  
  OBJECTIVE
  The purpose of the study was to develop and characterize a thermosensitive ophthalmic in situ nanogel of CUR-CNLC (CUR-CNLC-GEL) and evaluate in vitro and in vivo properties of the formulations.
  
  
  METHODS
  The physicochemical properties, in vitro release and corneal permeation, were evaluated. Ocular irritation and preocular retention capacity were also conducted. Finally, pharmacokinetic study in the aqueous humor was investigated by microdialysis technique.
  
  
  RESULTS
  The solution-gel transition temperature of the optimized formulation diluted by simulated tear fluid was 34 ± 1.0 °C. The CUR-CNLC-GEL displayed zero-order release kinetics. The apparent permeability coefficient (Papp) and the area under the curve (AUC0→∞) of CUR-CNLC-GEL were 1.56-fold and 9.24-fold, respectively, than those of curcumin solution (CUR-SOL, p < 0.01). The maximal concentration (Cmax) was significantly improved (p < 0.01). The prolonged mean residence time (p < 0.01) indicated that CUR-CNLC-GEL is a controlled release formulation.
  
  
  CONCLUSIONS
  Those results demonstrated that CUR-CNLC-GEL could become a potential formulation for increasing the bioavailability of CUR in the aqueous humor by enhancing corneal permeation and retention capacity.
authors.affiliation: a School of Traditional Chinese Materia Medica and.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: a School of Traditional Chinese Materia Medica and.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: b Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine , Tianjin , P.R. China , and.
authors.forename: Shiming
authors.initials: S
authors.lastname: Fang
authors.affiliation: a School of Traditional Chinese Materia Medica and.
authors.forename: Shuting
authors.initials: S
authors.lastname: Wang
authors.affiliation: a School of Traditional Chinese Materia Medica and.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chen
authors.affiliation: a School of Traditional Chinese Materia Medica and.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xiao
authors.affiliation: c Center for Drug Evaluation Research, Tianjin Institute of Pharmaceutical Research , Tianjin , P.R. China.
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D003474:Curcumin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation / Q000187:drug effects / Q000502:physiology; D000080385:Nanogels; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D013696:Temperature
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D000080385:Nanogels; D009883:Ophthalmic Solutions; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D003474:Curcumin
keywords: Cationic nanostructured lipid carriers; microdialysis; ocular drug delivery; pharmacokinetics; thermosensitive in situ nanogel