Interstitial continuous infusion therapy in a malignant glioma model in rats
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Local direct delivery of chemotherapeutic agents for the treatment of brain tumors is an area of focus in the development of new therapeutic paradigms. These techniques need improvement, especially in terms of drug retention in brain tissue.
Materials and methods
In this study, we used a rat glioma model to examine carboplatin distribution, as measured by platinum penetration, after delivery via interstitial continuous (i.c.) infusion. We also examined rat survival times in response to carboplatin and oxaliplatin. I.C. infusion, a modified version of convection-enhanced delivery (CED) for local drug delivery, uses low volume (1 μl per hour) continuous infusion directly into the tumor.
I.C. infusion produced a nearly 360-fold higher concentration of platinum in tumor tissue and significantly prolonged rodent survival time compared to intraperitoneal (i.p.) infusion.
We showed i.c. infusion allows for circumvention of the blood–brain barrier, focused drug distribution, and sustained drug delivery. This method could be a promising strategy for treating brain tumors.
KeywordsConvection-enhanced delivery Carboplatin Oxaliplatin Chemotherapy Rat model
This project was supported by the Rory David Deutsch Foundation, the Neuro-Oncology Research Foundation of Children’s Memorial Hospital, Chicago, Illinois and the Dr. Ralph and Marian C. Falk Medical Research Trust, Chicago, Illinois. We acknowledge expert technical assistance provided by Christopher D. McCabe, M.S. and Julianne Holleran (Medicine and Pharmacology, University of Pittsburgh Cancer Institute, Pittsburgh), The Department of Pathology Laboratory and Medicine, Children’s Memorial Hospital, Chicago, Illinois, and the editorial assistance of Rishi Lulla, M.D. and Ms. Terrie Byrne.
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