Abstract

The efficient delivery of a therapeutic agent to its site of action is a challenging, multifaceted bioengineering problem that is particularly complex in the treatment of cancer. We propose to develop a minimally invasive drug delivery system for cancer chemotherapy by using a multidisciplinary approach uniting research in cancer biology, interventional radiology and targeted drug delivery. Specifically, this project focuses on the development of functional polymer matrixes for image guided, site-specific, delivery of chemotherapeutic drugs. This comprehensive, functional delivery system will consist of 1) a biodegradable, biocompatible, injectable polymer matrix; 2) a sensitizing and release-modulating polymer; 3) a radiopaque agent allowing visualization with computed tomography or magnetic resonance imaging to facilitate image guided, site- specific placement and characterization; and 4) an active agent, or therapeutic, suited to the specifd. Once adequately chracterized, the components will be combined into the final delivery system, and cytotoxicity of the approach will be quantified in vitro using a rat colorectal carcinoma. The optimized device will then be used to deliver carboplatin to experimental rat tumors and the efficacy and mechanism of action of the system will be assessed. This multidisciplinary partnership will result in the development of a highly effective delivery system for site-specific treatment of cancer, demonstrate the potential of medical imaging in chemotherapy, and lead to the of enhanced understanding of cancer and paths leading to its eradication. Although the present focus centers on cancer treatment, if the efficacy of this approach is sufficiently demonstrated, the same concepts can be applied to enhance other minimally invasive, image guided procedures. Examples include enhancing radiofrequency ablation by delivering sodium chloride to increase tissue conductivity, improving successes of image guided biopsy by delivering hemostasis agents to control bleeding, and creating biodegradable, radiopaque markers for radiation therapy planning and guidance. ? ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA118399-03
Application #
7479737
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Tandon, Pushpa
Project Start
2006-08-01
Project End
2011-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
3
Fiscal Year
2008
Total Cost
$266,286
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Solorio, Luis; Wu, Hanping; Hernandez, Christopher et al. (2016) Ultrasound-guided intratumoral delivery of doxorubicin from in situ forming implants in a hepatocellular carcinoma model. Ther Deliv 7:201-12
Solorio, Luis; Exner, Agata A (2015) Effect of the Subcutaneous Environment on Phase-Sensitive In Situ-Forming Implant Drug Release, Degradation, and Microstructure. J Pharm Sci 104:4322-4328
Solorio, Luis; Sundarapandiyan, Divya; Olear, Alex et al. (2015) The Effect of Additives on the Behavior of Phase Sensitive In Situ Forming Implants. J Pharm Sci 104:3471-80
Ketchart, W; Smith, K M; Krupka, T et al. (2013) Inhibition of metastasis by HEXIM1 through effects on cell invasion and angiogenesis. Oncogene 32:3829-39
Solorio, Luis; Olear, Alexander M; Hamilton, Jesse I et al. (2012) Noninvasive characterization of the effect of varying PLGA molecular weight blends on in situ forming implant behavior using ultrasound imaging. Theranostics 2:1064-77
Solorio, Luis; Olear, Alexander M; Zhou, Haoyan et al. (2012) Effect of cargo properties on in situ forming implant behavior determined by noninvasive ultrasound imaging. Drug Deliv Transl Res 2:45-55
Krupka, Tianyi M; Exner, Agata A (2011) Structural parameters governing activity of Pluronic triblock copolymers in hyperthermia cancer therapy. Int J Hyperthermia 27:663-71
Patel, Ravi B; Solorio, Luis; Wu, Hanping et al. (2010) Effect of injection site on in situ implant formation and drug release in vivo. J Control Release 147:350-8
Solorio, Luis; Babin, Brett M; Patel, Ravi B et al. (2010) Noninvasive characterization of in situ forming implants using diagnostic ultrasound. J Control Release 143:183-90
Krupka, Tianyi M; Solorio, Luis; Wilson, Robin E et al. (2010) Formulation and characterization of echogenic lipid-Pluronic nanobubbles. Mol Pharm 7:49-59

Showing the most recent 10 out of 12 publications