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Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods
Author(s) -
Weinberg Brent D.,
Ai Hua,
Blanco Elvin,
Anderson James M.,
Gao Jinming
Publication year - 2007
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.30914
Subject(s) - doxorubicin , plga , materials science , histology , penetration (warfare) , distribution (mathematics) , drug delivery , biomedical engineering , medicine , pathology , chemotherapy , surgery , nanotechnology , nanoparticle , mathematical analysis , mathematics , operations research , engineering
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 μg/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. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res 2007