title: Characterization of a microsphere formulation containing glucose oxidase and its in vivo efficacy in a murine solid tumor model.
abstract: OBJECTIVE
  This work focused on the characterization and in vitro/in vivo evaluation of an alginate/chitosan microsphere (ACMS) formulation of glucose oxidase (GOX) for the locoregional delivery of reactive oxygen species for the treatment of solid tumors.
  
  
  METHODS
  The GOX distribution and ACMS composition were determined by confocal laser scanning microscopy and X-ray photoelectron spectroscopy. The mechanism of GOX loading and GOX-polymer interactions were examined with Fourier transform infrared spectroscopy and differential scanning calorimetry. In vitro cytotoxicity and in vivo efficacy of GOX-encapsulated ACMS (ACMS-GOX) were evaluated in EMT6 breast cancer cells and solid tumors.
  
  
  RESULTS
  GOX was loaded into calcium alginate (CaAlg) gel beads via electrostatic interaction and the CaAlg-GOX-chitosan complexation likely stabilized GOX. Higher concentrations of GOX near the surface of ACMS were detected. GOX retained its integrity upon adsorption to CaAlg gel beads during the coating and after release from ACMS. ACMS-GOX exhibited cytotoxicity to the breast cancer cells in vitro and their efficacy increased with increasing incubation time. Intratumorally delivered ACMS-GOX significantly delayed tumor growth with much lower general toxicity than free GOX.
  
  
  CONCLUSIONS
  The results suggest that the ACMS-GOX formulation has the potential for the intratumoral delivery of therapeutic proteins to treat solid tumors.
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada.
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.forename: Andrew Michael
authors.initials: AM
authors.lastname: Rauth
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.forename: Karlo
authors.initials: K
authors.lastname: Babakhanian
authors.forename: Xinyue
authors.initials: X
authors.lastname: Wang
authors.forename: Reina
authors.initials: R
authors.lastname: Bendayan
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Wu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D005949:Glucose Oxidase / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D005949:Glucose Oxidase
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