Pressure-Enabled Drug Delivery (PEDD) with SmartValve has been shown in small prospective and retrospective clinical studies to improve therapy uptake and tumor response.1,2

Overcoming solid stress and intra-tumoral pressure (ITP) is key to enabling therapeutic delivery.3,4

Infographic: 1. Interstitial Fluid Pressure (IFP). Elevated IFP limits the ability of drugs to leave blood vessels and deeply penetrate the tumor tissue.5 2. Solid Stress. Solid stress collapses blood vessels, preventing anticancer drugs from reaching malignant cells downstream.3 High Intra-Tumoral Pressure.
Infographic: 1. Interstitial Fluid Pressure (IFP). Elevated IFP limits the ability of drugs to leave blood vessels and deeply penetrate the tumor tissue.5 2. Solid Stress. Solid stress collapses blood vessels, preventing anticancer drugs from reaching malignant cells downstream.3 High Intra-Tumoral Pressure.

Elevated Interstitial fluid pressure (IFP) limits the ability of drugs to leave blood vessels and deeply penetrate the tumor tissue.5 The resulting heterogeneous intra-tumoral distribution of drugs is correlated with poor prognosis.5,6

There are multiple contributing factors:
Leaky blood vessels cause fluid to seep into the interstitial space with no way out.4

The lymphatic system within tumors is often underdeveloped and cannot drain fluids away.4

Elevated IFP reduces the pressurized movement of fluid from the vessel into the tissue, one mechanism thought to prevent therapeutics from penetrating the tumor mass.4,7

Solid Stress collapses blood vessels, preventing anticancer drugs from reaching malignant cells downstream.3

  • Tumors are made up of malignant cells, stromal cells, and blood/lymph vessels, all embedded in fibrous material known as the extracellular matrix (ECM).8
  • The proliferation of the ECM and cells results in the development of solid stress.8
  • Solid stress compresses vessels, which may reduce or halt blood flow to many parts of the tumor.8

The ECM and cells can reduce or stop blood flow, limiting drug delivery within the tumor mass.8

SmartValve technology works to help control flow and modulate pressure.

SmartValve is the only technology designed to:

  • Work in sync with the cardiac cycle.9*
  • Preserve more than 70% of forward blood flow with a pulsative response vs total occlusion due to its intermittently occlusive design.9,10†
  • Physiologically and atraumatically increase local vascular pressure at the target location close to the tumor.11‡
  • Infuse therapeutics into resistive tumor vessels to enable deeper perfusion and improve therapeutic delivery.1

Study Designs

*Ultrasound was employed in a porcine model to image tip performance in relation to the cardiac cycle.9
†Simulated bench testing in 1.5 mm vessel at 14 mL/min.10
‡Pressure wire introduced during planning angiogram to measure pressure of PEDD with SmartValve tip collapsed, expanded and during high-pressure saline flush.11

Review clinical data

PEDD with SmartValve technology modulates pressure to improve therapy uptake and tumor response.

Without PEDD
In traditional drug delivery, cardiac output flows through the hepatic and lobar arteries, but significant portions of the tumor are not perfused.12

For illustrative purposes.

With PEDD
PEDD is a novel approach that increases intravascular pressure, which may help open collapsed vessels in the tumor to enable deeper perfusion.1,13

For illustrative purposes.

An example of clinical pressure measurement.

A patient demonstration showed that SmartValve increased pressure above the baseline mean arterial pressure. The amount of pressure generated was controlled by the infusion rate to direct therapy into the tumor.11

In a single patient, intra-arterial measurement demonstrated the generation of controllable pressure by PEDD with SmartValve.11

Study Design

Single patient infusion with Pancreatic Infusion System. Pressure continuously monitored during initial positioning at target site, deployment of the PEDD device, and infusion of 3 cc saline bolus.11

See how it works
Graph Representation of Patient Mapping Procedure in a Clinical Trial

Standard procedures are limited in their ability to address the high ITP of solid tumors.14,15

Standard Microcatheter

In a simulation model with standard end-hole (EH) microcatheters, infusion pressure was not increased above systemic pressure.16*

Balloon Catheter

The deployment of a balloon stops blood flow and reduces pressure to the distal vasculature.17 The lack of blood flow during infusion of therapeutic agents may impact distribution and uptake in target tissues.18†

Study Designs

*Mathematical and physical simulation model of blood flow kinetics and pressure.16
†Matched infusions of Lipiodol in porcine kidney (n = 4) with PEDD device, balloon catheter, and microcatheter.18

Let us tell you more.

Contact us to learn more about this improved technology for the proprietary PEDD approach.

References

1. Titano JJ, Fischman AM, Cherian A, et al. End-hole Versus Microvalve Infusion Catheters in Patients Undergoing Drug-Eluting Microspheres-TACE for Solitary Hepatocellular Carcinoma Tumors: A Retrospective Analysis. Cardiovasc Intervent Radiol. 2019;42(4):560-568. 2. Pasciak AS, McElmurray JH, Bourgeois AC, Heidel RE, Bradley YC. The impact of an antireflux catheter on target volume particulate distribution in liver-directed embolotherapy: a pilot study. J Vasc Interv Radiol. 2015;26(5):660-669. 3. Stylianopoulos T, Martin JD, Chauhan VP, et al. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proc Natl Acad Sci U S A. 2012;109(38):15101-15108. 4. Sheth RA, Hesketh R, Kong DS, Wicky S, Oklu R. Barriers to drug delivery in interventional oncology. J Vasc Interv Radiol. 2013;24(8):1201-1207. 5. Heldin CH, Rubin K, Pietras K, Ostman A. High interstitial fluid pressure – an obstacle in cancer therapy. Nat Rev Cancer. 2004;4(10):806-813. 6. Kim HG, Yu AR, Lee JJ, Lee YJ, Lim SM, Kim JS. Measurement of Tumor Pressure and Strategies of Imaging Tumor Pressure for Radioimmunotherapy. Nucl Med Mol Imaging. 2019;53(4):235-241. 7. Jain RK, Stylianopoulos T. Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol. 2010;7(11):653-664. 8. Jain RK. An indirect way to tame cancer. Sci Am. 2014;310(2):46-53. 9. Data on file (animal study video). TriSalus Life Sciences®, 2019. 10. Data on file (510K). TriSalus Life Sciences®, 2019. 11. Data on file (CEA 001 trial). TriSalus Life Sciences®, 2019. 12. Jain RK. Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J Clin Oncol. 2013;31(17):2205-2218. 13. Data on file (REP-0362). TriSalus Life Sciences®, 2021. 14. Guan YS, He Q, Wang MQ. Transcatheter arterial chemoembolization: history for more than 30 years. ISRN Gastroenterol. 2012;2012:480650. 15.  Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019;380(15):1450-1462. 16. Durham E, Jaroch D, Hunter K. Poster presented at: World Conference on Interventional Oncology (WCIO); May 6-9, 2015; New York, NY. 17. Sniper® Balloon Occlusion Microcatheter, Instructions for Use. Embolx. http://embolx.com/wp-content/uploads/2018/08/Sniper-IFU-4.pdf. Accessed December 18, 2019. 18. Data on file. TriSalus Life Sciences®, 2019. 19. TriSalus™ TriNav® Infusion System, Instructions for Use.