The objective of this proposal is to demonstrate the feasibility of an innovative injection device (proposed product) to improve upon intratumoral delivery of liver therapeutics as compared to standard injection needles currently used. Hepatocelluar carcinoma (HCC) will become an increasing burden on economic resources in the coming years as the prevalence of cirrhosis due to multiple disease processes in the general population increases. Transplant and surgical treatment are well established and have provided satisfactory overall survival for eligible patients, however only a small minority of HCC patients are eligible for these therapies. Therefore considerable efforts have been directed toward developing alternative minimally invasive treatments. HCC therapeutic delivery by direct injection has the potential to significantly reduce the expense and morbidity of current therapeutics or those in development. Though direct injection is a seemingly straightforward approach to the problem, limited ability to inject tumors greater than 3cm in diameter and uneven distribution of the therapeutic after injection, are significant drawbacks to direct injectin. In contrast to conventional injection needles, the proposed injection device is porous along the entire length of the targeted anatomy; therefore, the surface area of tissue in contact with infusate is considerably increased. Hypothesis: Improved infusate delivery will lead to a larger area and more uniform distribution of infusate within the tumor tissue and lend itself to enhanced therapeutic direct intratumoral injection protocols for various chemoablative and anti- neoplastic infusates. Preliminary Data: We have demonstrated that porous injection devices have significantly improved in vivo distribution of ethanol within normal canine prostates and other studies have demonstrated the unique performance benefits of applicant's porous injection device.
Specific Aim : This project entails preclinical testing of the porous injection device for eventual application to human patients with intrahepatic tumors.
Aim 1. Demonstrate that the porous injection device provides broader distribution of an infusate compared to a standard needle. Task 1 - Transfer of VX-2 Cells and growth of tumor in rabbit for tumor implant tissue. Task 2 - Determine the preferred flow rate for infusate into the VX-2 tumor in rabbit liver Task 3 - Comparison of concentration and distribution of infusate components after infusion into VX-2 tumor with porous device and standard needle. Milestone: The porous injection device will show 50% greater distribution as compared to needle injection.

Public Health Relevance

Effective drug delivery of therapeutic agents directly into avascular regions of solid tumors is challenging with current clinical methodologies. The Applicants have developed novel porous hollow fiber catheters, which have the potential to demonstrate more uniform and better distribution of an infusate into solid tumor tissue than standard of care needles. In this project, animal studies will be conducted, to compare the PHFC to standard needle for infusate delivery into a liver cancer animal model.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Narayanan, Deepa
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Twin Star Tds, LLC
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Brady, Martin L; Raghavan, Raghu; Mata, Jaime et al. (2018) Large-Volume Infusions into the Brain: A Comparative Study of Catheter Designs. Stereotact Funct Neurosurg 96:135-141