title: Comparing routes of delivery for nanoliposomal irinotecan shows superior anti-tumor activity of local administration in treating intracranial glioblastoma xenografts.
abstract: BACKGROUND
  Liposomal drug packaging is well established as an effective means for increasing drug half-life, sustaining drug activity, and increasing drug efficacy, whether administered locally or distally to the site of disease. However, information regarding the relative effectiveness of peripheral (distal) versus local administration of liposomal therapeutics is limited. This issue is of importance with respect to the treatment of central nervous system cancer, for which the blood-brain barrier presents a significant challenge in achieving sufficient drug concentration in tumors to provide treatment benefit for patients.
  
  
  METHODS
  We compared the anti-tumor activity and efficacy of a nanoliposomal formulation of irinotecan when delivered peripherally by vascular route with intratumoral administration by convection-enhanced delivery (CED) for treating intracranial glioblastoma xenografts in athymic mice.
  
  
  RESULTS
  Our results show significantly greater anti-tumor activity and survival benefit from CED of nanoliposomal irinotecan. In 2 of 3 efficacy experiments, there were animal subjects that experienced apparent cure of tumor from local administration of therapy, as indicated by a lack of detectable intracranial tumor through bioluminescence imaging and histopathologic analysis. Results from investigating the effectiveness of combination therapy with nanoliposomal irinotecan plus radiation revealed that CED administration of irinotecan plus radiation conferred greater survival benefit than did irinotecan or radiation monotherapy and also when compared with radiation plus vascularly administered irinotecan.
  
  
  CONCLUSIONS
  Our results indicate that liposomal formulation plus direct intratumoral administration of therapeutic are important for maximizing the anti-tumor effects of irinotecan and support clinical trial evaluation of this therapeutic plus route of administration combination.
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, 1450 Third Street, Room HD-283, San Francisco, CA 94158, USA.
authors.forename: Pin-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ozawa
authors.forename: Daryl C
authors.initials: DC
authors.lastname: Drummond
authors.forename: Ashish
authors.initials: A
authors.lastname: Kalra
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Fitzgerald
authors.forename: Dmitri B
authors.initials: DB
authors.lastname: Kirpotin
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
authors.forename: Nicholas
authors.initials: N
authors.lastname: Butowski
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.forename: John R
authors.initials: JR
authors.lastname: Forsayeth
authors.forename: Krystof
authors.initials: K
authors.lastname: Bankiewicz
authors.forename: C David
authors.initials: CD
authors.lastname: James
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018481:Convection; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D049690:History, Ancient; D006801:Humans; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D000077146:Irinotecan; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D000077146:Irinotecan; D002166:Camptothecin