Local release of dexamethasone from polymer millirods effectively prevents fibrosis after radiofrequency ablation.
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.
Blanco
Elvin
E
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Weinberg
Brent D
BD
Stowe
Nicholas T
NT
Anderson
James M
JM
Gao
Jinming
J
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials; D017115:Catheter Ablation; D003907:Dexamethasone / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004343:Drug Implants; D005355:Fibrosis; D006801:Humans; D066298:In Vitro Techniques; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D047392:beta-Cyclodextrins
D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D004343:Drug Implants; D011108:Polymers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone