Intra-arterial administration of peptide-drug conjugates for tumor-selective drug delivery

This technology is an intra-arterial drug delivery system in which sort cationic peptides are linked to cancer therapeutics, allowing the drugs to cross the blood-brain barrier and target negatively-charged solid tumors.

Unmet Need: Strategy to maintain high positive charge on drug delivery vectors in the blood

Tumor cell membranes are frequently negatively-charged due to overexpression of anionic lipids on the surface. As a result, cationic peptides such as trans-activating transcription factors (TAT) have been implemented as drug delivery vectors to target and penetrate tumor cells. However, intravenous (IV) administration of cationic delivery vectors can attenuate their surface charge due to interactions with serum proteins and immune cells in the blood, which diminishes their targeting capacity. As such, there is a need for a method that delivers peptide-drug conjugates while maintaining their tumor-penetrating positive charge.

The Technology: Intra-arterial flow arrest delivery strategy mitigates charge attenuation in the blood

This technology is an improved delivery method for peptide-drug conjugates that works by inducing a transient cardiac arrest (flow arrest) followed by injection of the cationic peptide-drug therapeutic into an artery (intra-arterial) in close proximity to the tumor of interest. Unlike IV administration that causes attenuation of the positively-charged peptide-drug conjugate, flow arrest intra-arterial delivery minimizes exposure of the delivery vehicle to elements in the blood that can decrease the delivery agent’s cationic nature and ability to target tumors. Consequently, this technology maintains the tumor-penetrating positive charge on the peptide-drug conjugate, enabling improved delivery of the therapeutic to the tumor of interest.

This technology has been validated in human cancer cell lines and in animal models.

Applications:

• Drug delivery to solid tumors
• Drug delivery across the blood brain barrier for neurological disorders
• Administration of therapeutics that are unstable in blood
• Delivery of therapeutic drugs to apoptotic cells

Advantages:

• Maintains high cationic charge of the peptide-drug conjugate by minimizing exposure to blood
• Cationic peptides readily cross the blood-brain barrier
• Drug delivery vehicles can hold large amounts of therapeutic cargo
• Robust tumor-selective uptake

Lead Inventor:

Shailendra Joshi, MD

Patent Information:

Patent Pending

Related Publications:

• Nguyen J, Hossain SS, Cookie JRN, Ellis JA, Deci MB, Emala CW, Bruce JN, Bigio IJ, Straubinger RM, Joshi S. “Flow arrest intra-arterial delivery of small TAT-decorated and neutral micelles to gliomas” Journal of Neuro-Oncology. 2017 Apr 18; 133(1): 77-85.

• Joshi S, Cooke JRN, Ellis JA, Emala CW, Bruce JN. “Targeting brain tumors by intra-arterial delivery of cell-penetrating peptides: a novel approach for primary and metastatic brain malignancy” J Neurooncol. 2017 Dec; 135(3): 497-506.

Tech Ventures Reference:

• IR CU17144

• Licensing Contact: Sara Gusik