This research effort is a long-term commitment to develop intratumoral drug delivery as a local chemotherapy to supplement twnor thermoablation for the treatment of liver cancers. In this treatment, image-guided thermoablation first destroys the majority of the tumor tissue by heat. The drug delivery device, in the shape of a cylindrical millirod, is then implanted into the thermoablated tumors to kill any cancer cells remaining after thermoablation. The objective of the proposed application is to develop and evaluate drug delivery systems that can modulate the release of doxorubicin, an anticancer drug, for intratumoral drug delivery to thermoablated tumor tissues. The central hypothesis is that polymer millirods with dual release kinetics-an initial burst release followed by a sustained release of drugs-can provide the maximal therapeutic effect to supplement thermoablation in the treatment of liver tumors. To test this central hypothesis, we will carry out the following four specific aims: (1) rational design of polymer millirods with dual release kinetics by mathematical models; (2) development and characterization of polymer millirods with dual release kinetics; (3) pharmacokinetic analysis of implanted polymer millirods in rabbit VX-2 liver tumors; (4) validation of drug efficacy by monitoring of tumor size and histology analysis. Successful execution of the proposed application will establish a solid pharmacological basis and bioengineering foundation for the development of drug delivery systems for intratumoral drug delivery. In combination with image-guided thermoablation, this therapeutic procedure should provide an innovative, minimally invasive and less toxic therapy for the treatment of liver tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090696-02
Application #
6624152
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Fu, Yali
Project Start
2002-05-09
Project End
2006-04-30
Budget Start
2003-05-15
Budget End
2004-04-30
Support Year
2
Fiscal Year
2003
Total Cost
$306,383
Indirect Cost
Name
Case Western Reserve University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Dong, Ying; Chin, Shook-Fong; Blanco, Elvin et al. (2009) Intratumoral delivery of beta-lapachone via polymer implants for prostate cancer therapy. Clin Cancer Res 15:131-9
Weinberg, Brent D; Patel, Ravi B; Wu, Hanping et al. (2008) Model simulation and experimental validation of intratumoral chemotherapy using multiple polymer implants. Med Biol Eng Comput 46:1039-49
Weinberg, Brent D; Blanco, Elvin; Gao, Jinming (2008) Polymer implants for intratumoral drug delivery and cancer therapy. J Pharm Sci 97:1681-702
Blanco, Elvin; Bey, Erik A; Dong, Ying et al. (2007) Beta-lapachone-containing PEG-PLA polymer micelles as novel nanotherapeutics against NQO1-overexpressing tumor cells. J Control Release 122:365-74
Weinberg, Brent D; Patel, Ravi B; Exner, Agata A et al. (2007) Modeling doxorubicin transport to improve intratumoral drug delivery to RF ablated tumors. J Control Release 124:11-9
Sutton, Damon; Wang, Shihu; Nasongkla, Norased et al. (2007) Doxorubicin and beta-lapachone release and interaction with micellar core materials: experiment and modeling. Exp Biol Med (Maywood) 232:1090-9
Sutton, Damon; Nasongkla, Norased; Blanco, Elvin et al. (2007) Functionalized micellar systems for cancer targeted drug delivery. Pharm Res 24:1029-46
Weinberg, Brent D; Blanco, Elvin; Lempka, Scott F et al. (2007) Combined radiofrequency ablation and doxorubicin-eluting polymer implants for liver cancer treatment. J Biomed Mater Res A 81:205-13
Weinberg, Brent D; Ai, Hua; Blanco, Elvin et al. (2007) Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods. J Biomed Mater Res A 81:161-70
Wang, Fangjing; Saidel, Gerald M; Gao, Jinming (2007) A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding. J Control Release 119:111-20

Showing the most recent 10 out of 23 publications