title: Sustained-release G-CSF microspheres using a novel solid-in-oil-in-oil-in-water emulsion method.
abstract: BACKGROUND
  The main treatments for cancers are still chemotherapy and radiotherapy for intermediate-stage cancer and terminal cancer. However, the therapeutic methods often result in a decreased neutrophilic granulocyte count and other side effects. In this study, in order to improve the neutrophilic granulocyte levels in the blood after radiotherapy and chemotherapy, we developed a sustained-release granulocyte colony-stimulating factor (G-CSF) microsphere formulation using a novel solid-in-oil-in-oil-in-water (S/O/O/W) emulsification method.
  
  
  METHODS
  G-CSF was loaded into dextran nanoparticles by freezing-induced phase separation, and then the G-CSF-loaded nanoparticles were encapsulated into sustained-release poly(lactic-co- glycolic acid) microspheres using S/O/O/W emulsification. The control microspheres were also prepared through W/O/W emulsification. The performance of the two microsphere formulations was investigated both in vitro and in vivo.
  
  
  RESULTS
  The microspheres for the controlled release of G-CSF in a zero-order or near-zero-order pattern were provided for 2 weeks. The in vitro cumulative G-CSF release kept over 90% of its bioactivity, which was proved by a NFS-60 cell line growth assay. The microspheres of the control group fabricated by W/O/W emulsification maintained less then half of its bioactivity. The in vivo efficacy of microspheres made using the S/O/O/W method was higher than those using the W/O/W method.
  
  
  CONCLUSIONS
  These results suggested that the microspheres prepared by the S/O/O/W method had increased neutrophil activity compared to those prepared by W/O/W.
authors.affiliation: Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Hong
authors.forename: Mier
authors.initials: M
authors.lastname: Jiang
authors.forename: Weien
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D003911:Dextrans / Q000737:chemistry; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D009821:Oils / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D003911:Dextrans; D004655:Emulsions; D009821:Oils; D014867:Water; D016179:Granulocyte Colony-Stimulating Factor