Overcoming the Blood-Brain Barrier to Taxane Delivery for Neurodegenerative Diseases and Brain Tumors

Antonie Rice, Mary L. Michaelis, Gunda Georg, Yanbin Liu, Brandon Turunen, Kenneth L. Audus

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


The blood-brain barrier (BBB) effectively prevents microtubule (MT)-stabilizing drugs from readily entering the central nervous system (CNS). Amajor limiting factor for microtubule-stabilizing drug permeation across the BBB is the active efflux back into the circulation by the overexpression of the multidrug-resistant gene product 1 (MDR1) or P-glycoprotein (P-gp). This study has focused on strategies to overcome P-gp-mediated efflux of Taxol analogs, MT-stabilizing agents that could be used to treat brain tumors and, potentially, neurodegenerative diseases such as Alzheimer's disease. However, taxol is a strong P-gp substrate that limits its distribution across the BBB and therapeutic potential in the CNS. We have found that addition of a succinate group to the C-10 position of paclitaxel (Taxol) results in an agent, Tx-67, with reduced interactions with P-gp and enhanced permeation across the BBB in both in vitro and in situ models. Our studies demonstrate the feasibility of making small chemical modifications to Taxol to generate analogs with reduced affinity for the P-gp but retention of MT-stabilizing properties, i.e., a taxane that may reach and treat therapeutic targets in the CNS.

Original languageEnglish (US)
Pages (from-to)339-343
Number of pages5
JournalJournal of Molecular Neuroscience
Issue number3
StatePublished - 2003

Bibliographical note

Funding Information:
This work was supported by the Institute for the Study of Aging (New York) and an NIH grant (NCI 1 RO1 CA82801).


  • Blood-brain barrier
  • Brain microcapillary endothelial cells
  • CNS drug permeation
  • Microtubule-stabilizing drugs
  • Neurofibrillary pathology
  • Taxol


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