title: Local delivery of interleukin-2 and adriamycin is synergistic in the treatment of experimental malignant glioma.
abstract: BACKGROUND
  Local delivery of adriamycin (ADR) via biodegradable polymers has been shown to improve survival in rats challenged intracranially with 9L gliosarcoma. Likewise, local delivery of interleukin-2 (IL-2) has been shown to extend survival in experimental brain tumor models. In the current study, we hypothesized that local delivery of ADR and IL-2 might act synergistically against experimental intracranial glioma.
  
  
  METHODS
  Polyanhydride polymers (PCPP-SA) containing 5% ADR by weight were prepared using the mix-melt method. IL-2 polymer microspheres (IL-2 MS) were produced via the complex coacervation of gelatin and chondroitin sulfate in the presence of IL-2. Sixty male Fisher 344 rats received an intracranial challenge with a lethal dose of 9L gliosarcoma cells. In addition, a group of rats were injected with either IL-2 MS or empty microspheres. Five days later they received ADR or blank polymer. There were a total of four treatment groups: (1) empty microspheres, blank polymer; (2) empty microspheres, ADR polymer; (3) IL-2 MS, blank polymer; and (4) IL-2 MS, ADR polymer.
  
  
  RESULTS
  Compared to control animals treated with empty microspheres and blank polymer, animals receiving empty microspheres and ADR polymer (P < 0.0004), IL-2 MS and blank polymer (P < 0.0005), and IL-2 MS combined with ADR polymer (P < 0.0000002) all showed statistically significant improvement in survival. In addition, animals receiving the IL-2/ADR combination had significantly extended survival compared to either ADR or IL-2 alone (P < 0.000003 and P < 0.0004, respectively).
  
  
  CONCLUSIONS
  Both ADR and IL-2, when delivered locally, are effective monotherapeutic agents against experimental intracranial gliosarcoma. The combination ADR and IL-2 therapy is more effective than either agent alone.
authors.affiliation: Departments of Neurosurgery and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Wesley
authors.initials: W
authors.lastname: Hsu
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
authors.forename: Betty
authors.initials: B
authors.lastname: Tyler
authors.forename: Henry
authors.initials: H
authors.lastname: Brem
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005260:Female; D018316:Gliosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015552:Injections, Intralesional; D007276:Injections, Intraventricular; D007376:Interleukin-2 / Q000008:administration & dosage; D008863:Microspheres; D011108:Polymers; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2; D011108:Polymers; D004317:Doxorubicin