Combined radiofrequency ablation and doxorubicin-eluting polymer implants for liver cancer treatment.
Previously, biodegradable polymer implants (polymer millirods) to release chemotherapeutic agents directly into tumors have been developed. The purpose of this study is to evaluate local drug distribution from these implants in liver tumors treated with radiofrequency (RF) ablation and determine if the implants provide a therapeutic improvement over RF ablation alone. Cylindrical implants were fabricated using 65% poly(D,L-lactide-co-glycolide) (PLGA), 21.5% NaCl, and 13.5% doxorubicin. Control or drug-containing millirods were implanted inside VX2 liver tumors (11 mm diameter) in rabbits after RF ablation. Therapeutic efficacy was assessed 4 and 8 days after treatment using tumor size, histology, and fluorescence measurement of drug distribution. Tumors in both test groups recurred at the boundary of the ablated region. Therapeutic doxorubicin concentrations were found in more than 80% of the ablated area, but concentrations declined rapidly at the boundary between normal and ablated tissue. This region was characterized by a developing fibrous capsule with resolving inflammation, which restricted drug transport out of the ablated zone. The intratumoral doxorubicin implants delivered high concentrations of drug within the ablated region but only limited amounts outside the ablation zone. Future studies will focus on overcoming the fibrotic transport barrier and enhancing drug delivery to the periphery of the ablation region to prevent tumor progression.
Weinberg
Brent D
BD
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
Blanco
Elvin
E
Lempka
Scott F
SF
Anderson
James M
JM
Exner
Agata A
AA
Gao
Jinming
J
D020341:Absorbable Implants; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D017115:Catheter Ablation; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004343:Drug Implants / Q000493:pharmacokinetics / Q000494:pharmacology*; D019344:Lactic Acid; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits
D000903:Antibiotics, Antineoplastic; D004343:Drug Implants; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin