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.
(c) 2005 Wiley Periodicals, Inc