title: 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.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Elvin
authors.initials: E
authors.lastname: Blanco
authors.forename: Brent D
authors.initials: BD
authors.lastname: Weinberg
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Stowe
authors.forename: James M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
mesh_terms: 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
chemical_list: 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