title: Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods.
abstract: The purpose of this study was to evaluate the antitumor efficacy and local drug distribution from doxorubicin-containing poly(D,L-lactide-co-glycolide) (PLGA) implants for intratumoral treatment of liver cancer in a rabbit model. Cylindrical polymer millirods (length 8 mm, diameter 1.5 mm) were produced using 65% PLGA, 21.5% NaCl, and 13.5% doxorubicin. These implants were placed in the center of VX2 liver tumors (n = 16, 8 mm in diameter) in rabbits. Tumors were removed 4 and 8 days after millirod implantation, and antitumor efficacy was assessed using tumor size measurements, tumor histology, and fluorescent measurement of drug distribution. The treated tumors were smaller than the untreated controls on both day 4 (0.17 +/- 0.06 vs. 0.31 +/- 0.08 cm(2), p = 0.048) and day 8 (0.14 +/- 0.04 vs. 1.8 +/- 0.8 cm(2), p = 0.025). Drug distribution profiles demonstrated high doxorubicin concentrations (>1000 microg/g) at the tumor core at both time points and drug penetration distances of 2.8 and 1.3 mm on day 4 and 8, respectively. Histological examination confirmed necrosis throughout the tumor tissue. Biodegradable polymer millirods successfully treated the primary tumor mass by providing high doxorubicin concentrations to the tumor tissue over an eight day period.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Brent D
authors.initials: BD
authors.lastname: Weinberg
authors.forename: Hua
authors.initials: H
authors.lastname: Ai
authors.forename: Elvin
authors.initials: E
authors.lastname: Blanco
authors.forename: James M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D019344:Lactic Acid / Q000138:chemical synthesis; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008422:Materials Testing; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy; D011100:Polyglycolic Acid / Q000138:chemical synthesis; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis; D011817:Rabbits; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin