Hyperosmotic intraventricular drug delivery of DV1 in the management of intracranial metastatic breast cancer in a mouse model

Satish Krishnamurthy; Jie Li; Alexa Bodman; Chaozai Zhang; Yilei Yang; Jing An

doi:10.1016/j.jocn.2019.01.003

Hyperosmotic intraventricular drug delivery of DV1 in the management of intracranial metastatic breast cancer in a mouse model

J Clin Neurosci. 2019 Apr:62:207-211. doi: 10.1016/j.jocn.2019.01.003. Epub 2019 Jan 21.

Authors

Satish Krishnamurthy¹, Jie Li², Alexa Bodman², Chaozai Zhang³, Yilei Yang⁴, Jing An⁵

Affiliations

¹ Department of Neurosurgery, Upstate Medical University, State University of New York (SUNY), 175 Elizabeth Blackwell Street Syracuse, NY 13210, USA. Electronic address: krishnsa@upstate.edu.
² Department of Neurosurgery, Upstate Medical University, State University of New York (SUNY), 175 Elizabeth Blackwell Street Syracuse, NY 13210, USA.
³ Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
⁴ Department of Pharmacology, Upstate Medical University, State University of New York (SUNY), 750 Adams Street, Syracuse, NY 13210, USA.
⁵ Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Pharmacology, Upstate Medical University, State University of New York (SUNY), 750 Adams Street, Syracuse, NY 13210, USA.

Abstract

Advances in therapies for breast cancer with cerebral metastases has been slow, despite this being a common diagnosis, due to limited drug delivery by the blood brain barrier. Improvements in drug delivery for brain metastasis to target the metastases and bypass the blood brain barrier are necessary. In our study, we delivered an inhibitor of chemokine receptor 4 by convection enhanced delivery in a hyperosmotic solution to prevent brain metastasis in a mouse model of metastatic breast cancer. We found the inhibitor limited metastatic disease and more interestingly, the hyperosmotic solution targeted tumor tissue allowing for a higher accumulation of the therapy into tumor tissue. This finding has the potential to improve delivery of chemotherapeutic agents to brain metastases.

Keywords: Brain metastasis; Breast cancer; CXCR4; Drug delivery; Hyperosmotic therapy.

MeSH terms

Animals
Antineoplastic Agents / administration & dosage*
Brain Neoplasms / secondary*
Cell Line, Tumor
Disease Models, Animal
Drug Delivery Systems / methods*
Female
Humans
Injections, Intraventricular
Mammary Neoplasms, Experimental / secondary*
Mice
Mice, Nude
Osmolar Concentration
Receptors, CXCR4 / antagonists & inhibitors*
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents
Receptors, CXCR4

Grants and funding

R01 GM057761/GM/NIGMS NIH HHS/United States