Local release of dexamethasone from polymer millirods effectively prevents fibrosis after radiofrequency ablation

Elvin Blanco, Brent D. Weinberg, Nicholas T. Stowe, James M. Anderson, Jinming Gao

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Recent studies show that after radiofrequency (RF) ablation, fibrosis occurs at the ablation boundary, hindering anticancer drug transport from a locally implanted polymer depot to the ablation margin, where tumors recur. The purpose of this study is to investigate strategies that can effectively deliver dexamethasone (DEX), an anti-inflammatory agent, to prevent fibrosis. Polymer millirods consisting of poly(D,L-lactide-co-glycolide) (PLGA) were loaded with either DEX complexed with hydroxypropyl β-cyclodextrin (HPβ-CD), or an NaCl and DEX mixture. In vitro release studies show that DEX complexed with HPβ-CD released 95% of the drug after 4 days, compared to 14% from millirods containing NaCl and DEX. Rat livers underwent RF ablation and received either DEX-HPβ-CD-loaded millirods, PLGA millirods with an intraperitoneal (i.p.) DEX injection, or control PLGA millirods alone. After 8 days in vivo, heightened inflammation and the appearance of a well-defined fibrous capsule can be observed in both the control experiments and those receiving a DEX injection (0.29 ± 0.08 and 0.26 ± 0.07 mm in thickness, respectively), with minimal inflammation and fibrosis present in livers receiving DEX millirods (0.04 ± 0.01 mm). Results from this study show that local release of DEX prevents fibrosis more effectively than a systemic i.p. injection.

Original languageEnglish (US)
Pages (from-to)174-182
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Volume76
Issue number1
DOIs
Publication statusPublished - Jan 2006

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Keywords

  • Dexamethasone
  • Fibrous capsule formation
  • Inflammation
  • Polymer implant
  • Radiofrequency ablation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials

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