title: Near-infrared image-guided delivery and controlled release using optimized thermosensitive liposomes.
abstract: OBJECTIVE
  To engineer optimized near-infrared (NIR) active thermosensitive liposomes to potentially achieve image-guided delivery of chemotherapeutic agents.
  
  
  METHODS
  Thermosensitive liposomes were surface-coated with either polyethylene glycol or dextran. Differential scanning calorimetry and calcein release studies were conducted to optimize liposomal release, and flow cytometry was employed to determine the in vitro macrophage uptake of liposomes. Indocyanine green (ICG) was encapsulated as the NIR dye to evaluate the in vivo biodistribution in tumor-bearing mice.
  
  
  RESULTS
  The optimized thermosensitive liposome formulation consists of DPPC, SoyPC, and cholesterol in the 100:50:30 molar ratio. Liposomes with dextran and polyethylene glycol demonstrated similar thermal release properties; however in vitro macrophage uptake was greater with dextran. Non-invasive in vivo NIR imaging showed tumor accumulation of liposomes with both coatings, and ex vivo NIR imaging correlated well with actual ICG concentrations in various organs of healthy mice.
  
  
  CONCLUSIONS
  The optimized thermosensitive liposome formulation demonstrated stability at 37 °C and efficient burst release at 40 and 42 °C. Dextran exhibited potential for application as a surface coating in thermosensitive liposome formulations. In vivo studies suggest that liposomal encapsulation of ICG permits reliable, real-time monitoring of liposome biodistribution through non-invasive NIR imaging.
authors.affiliation: Department of Pharmaceutical Sciences, Mercer University, Atlanta, Georgia 30341, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Turner
authors.forename: Delaram
authors.initials: D
authors.lastname: Moshkelani
authors.forename: Colby S
authors.initials: CS
authors.lastname: Shemesh
authors.forename: David
authors.initials: D
authors.lastname: Luc
authors.forename: Hailing
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D004396:Coloring Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics; D003911:Dextrans / Q000737:chemistry; D007208:Indocyanine Green / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000175:diagnosis; D010587:Phagocytosis; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties; D013696:Temperature; D014018:Tissue Distribution
chemical_list: D004396:Coloring Agents; D003692:Delayed-Action Preparations; D003911:Dextrans; D008081:Liposomes; D011092:Polyethylene Glycols; D007208:Indocyanine Green