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

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 beta-cyclodextrin (HPbeta-CD), or an NaCl and DEX mixture. In vitro release studies show that DEX complexed with HPbeta-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-HPbeta-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.