Polymer delivery of camptothecin against 9L gliosarcoma: Release, distribution, and efficacy

Phillip B. Storm, John L. Moriarity, Betty Tyler, Peter C Burger, Henry Brem, Jon Weingart

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Camptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro; unfortunately, systemic toxicity has limited its in vivo efficacy. This is the first study to investigate the release, biodistribution, and efficacy of camptothecin from a biodegradable polyanhydride polymer. Tritiated camptothecin was incorporated into biodegradable polymers that were implanted intracranially in 16 male Fischer 344 rats and the animals were followed up to 21 days post-implant. A concentration of 11-45 μg of camptothecin-sodium/mg brain tissue was within a 3 mm radius of the polymer disc, with levels of 0.1 μg at the outermost margin of the rat brain, 7 mm from the site of implantation. These tissue concentrations are within the therapeutic ranges for human and rat glioma lines tested against camptothecin-sodium in vitro. The in vivo efficacy of camptothecin-sodium was evaluated with male Fischer 344 rats implanted intracranially with 9L gliosarcoma and compared with the efficacy of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The animals were divided into four groups. Group 1 (control) had a median survival of 17 days. Group 2 (3.8% BCNU polymer) had a median survival of 23 days (P = 0.006). Group 3 (20% camptothecin polymer) had a median survival of 25 days (P = 0.023). Group 4 (50% camptothecin polymer) had a median survival of 69 days (P < 0.001). Drug loadings of 20% and 50% camptothecin released intact camptothecin for up to 1000 h in vitro. We conclude that the biodegradable polymer p(CPP: SA) releases camptothecin-sodium, produces tumoricidal tissue levels, results in little or no systemic toxicity, and prolongs survival in a rat glioma model.

Original languageEnglish (US)
Article number393672
Pages (from-to)209-217
Number of pages9
JournalJournal of neuro-oncology
Volume56
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Blood-brain barrier
  • Camptothecin
  • Distribution
  • Glioma
  • Polymer

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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