title: Effect of sucrose as a lyoprotectant on the integrity of paclitaxel-loaded liposomes during lyophilization.
abstract: BACKGROUND
  The stability of liposomes in the form of dispersion is a major concern due to drug leakage and fusion or aggregation. The stability can be improved by lyophilization, but the stress induced by the lyophilization process can affect the integrity of liposomes.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the lyoprotective effect of sucrose on drug leakage and vesicle size of paclitaxel-loaded liposomes during the lyophilization process.
  
  
  METHODS
  Paclitaxel-loaded liposomal dispersions were prepared with sucrose at several lipid-sugar ratios, and internal-external sugar ratios, and then lyophilized. The entrapped paclitaxel content and vesicle size were monitored before and after lyophilization. The stability of the formulation was evaluated at 5 and 25 °C.
  
  
  RESULTS
  A significant increase in free paclitaxel and vesicle size was observed with the liposomes lyophilized without sucrose. Inclusion of sucrose in the formulation significantly reduced the free paclitaxel concentration and minimized the changes in vesicle size. The extent of protection improved further when sucrose was also present in the internal portion of the bilayer. The lyophilized formulation was stable at 5 °C for 3 months.
  
  
  CONCLUSIONS
  A significant (p < 0.05) correlation was observed between free paclitaxel content and the average diameter of the liposomes with respect to sucrose concentrations in the formulation. Sucrose protected the liposomes from drug leakage and aggregation/fusion induced by the lyophilization process in a concentration dependent manner.
  
  
  CONCLUSIONS
  The integrity of paclitaxel-loaded liposomes was preserved during lyophilization by optimal levels of lyoprotectant sucrose in the formulation.
authors.affiliation: a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.
authors.forename: Vinayagam
authors.initials: V
authors.lastname: Kannan
authors.affiliation: a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.|b Plough Center for Sterile Drug Delivery Systems, The University of Tennessee Health Science Center , Memphis , TN , USA.
authors.forename: Pavan
authors.initials: P
authors.lastname: Balabathula
authors.affiliation: a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.|b Plough Center for Sterile Drug Delivery Systems, The University of Tennessee Health Science Center , Memphis , TN , USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Thoma
authors.affiliation: a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.
authors.forename: George C
authors.initials: GC
authors.lastname: Wood
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D005612:Freeze Drying; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes; D017239:Paclitaxel; D010316:Particle Size; D013395:Sucrose / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D013395:Sucrose; D017239:Paclitaxel
keywords: Freeze drying; lyoprotection; nanotechnology