title: Evaluation of biocompatibility and anti-glioma efficacy of doxorubicin and irinotecan drug-eluting bead suspensions in alginate.
abstract: BACKGROUND
  Chemotherapeutic drug-eluting beads (DEBs) are microspheres that are in clinical use for intraarterial chemoembolisation of liver cancer. Here we report on the biocompatibility and anti-tumour efficacy of DEBs after intratumoral application in a rat BT4Ca glioma model.
  
  
  RESULTS
  Doxorubicin and irinotecan-eluting DEBs were suspended in a Ca(2+)-free aqueous alginate solution that provides a sol-gel transition when injected into the Ca(2+) rich brain tissue. In this way the DEBs are immobilised at the implantation site. Forced elution studies in vitro using a USP-4 flow-through apparatus demonstrated that the alginate excipient helped to reduce the burst effect and rate the elution from the beads. From the in vivo evaluation, doxorubicin DEBs demonstrated a significant local toxicity, while irinotecan-loaded DEBs showed good local tissue compatibility. Doxorubicin at higher concentrations and irinotecan-loaded DEBs were found to decrease tumour volume, increase survival time and decrease the Ki67 proliferation index of the tumour. Doxorubicin was shown by fluorescent microscopy to diffuse into the peritumoral tissue, but also penetrates along white matter tracts, to more distant areas.
  
  
  CONCLUSIONS
  We conclude that the alginate suspension of irinotecan DEBs can be considered safe and effective in a clinical setting.
authors.affiliation: Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
authors.forename: Patricia
authors.initials: P
authors.lastname: Mertens
authors.forename: Steffen
authors.initials: S
authors.lastname: Baltes
authors.forename: Peter
authors.initials: P
authors.lastname: Geigle
authors.forename: Thomas
authors.initials: T
authors.lastname: Brinker
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D000077146:Irinotecan; D008297:Male; D008422:Materials Testing; D008863:Microspheres; D051381:Rats; D015996:Survival Rate; D013535:Suspensions; D047368:Tumor Burden
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D013535:Suspensions; D000077146:Irinotecan; D004317:Doxorubicin; D020723:Glucuronic Acid; D002166:Camptothecin