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Heuristic modeling of drug delivery to malignant brain tumors

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Abstract

It is apparent that chemotherapy against malignant brain tumors is generally ineffective. While some agents are more effective than others, none appreciably alters the clinical course of and the poor prognosis for patients with brain tumors. Even though new and more effective agents are being or will be developed, chemotherapy depends as much on the delivery of drug as it does on the drug used. Therefore, we have defined factors that we believe are of primary importance in drug delivery to brain tumors, and, using computer simulation, we have modeled the effects of these factors. In this article we discuss (a) the extent of the “breakdown” in the blood-brain barrier (BBB) that accompanies the development of malignant tumors in the brain, (b) factors that influence drug transport from tumor capillaries to tumor cells at varying distances from the capillaries, (c) the problems inherent in drug delivery from a well-vascularized tumor outward to normal brain tissue that might harbor malignant cells but that does not have leaky vessels (i.e., normal BBB), and (d) the difficulties in drug delivery from a well-perfused, highly permeable outer tumor shell to a central, poorly perfused tumor core.

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Authors and Affiliations

  1. Brain Tumor Research Center, Department of Neurological Surgery, and the Departments of Neurology and Pharmaceutical Chemistry, Schools of Medicine and Pharmacy, University of California, 94143, San Francisco, California

    Victor A. Levin

  2. Theoretical Statistics and Mathematics Branch, National Institute of Mental Health, National Institutes of Health, 20205, Bethesda, Maryland

    Clifford S. Patlak

  3. Department of Biophysics and Biomathematics, School of Medicine, University of California, 94143, San Francisco, California

    Herbert D. Landahl

Authors
  1. Victor A. Levin
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  2. Clifford S. Patlak
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  3. Herbert D. Landahl
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Additional information

This work was supported by American Cancer Society Grant CH-75 and NIH Program Project Grant CA-13525. V. A. L. is the recipient of an American Cancer Society Faculty Research Award (FRA-155).

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Levin, V.A., Patlak, C.S. & Landahl, H.D. Heuristic modeling of drug delivery to malignant brain tumors. Journal of Pharmacokinetics and Biopharmaceutics 8, 257–296 (1980). https://doi.org/10.1007/BF01059646

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