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Drug Delivery

Drug Delivery - Poster Session A

Poster J4 - Characterizing Extracellular Matrix Paste for Localized Immunotherapy Delivery

Thursday, October 24, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Currently approved cancer immunotherapies utilize intravenous infusion to deliver potent immunotherapeutics. However, this type of systemic delivery leads to overactivation of the immune system. A more effective approach may be to deliver and maintain immunotherapeutics within a solid tumor. This method aims to increase the concentration of the immunotherapy medicine at the tumor site while minimizing the adverse effects associated with systemic exposure. This project explores the use of an extracellular matrix (ECM) paste as a delivery medium for immunotherapy in order to enhance intratumoral retention. The three objectives of this project are: 1) to understand the parameters necessary to formulate an ECM paste, 2) to determine an efficient method to load the paste into a syringe, and 3) to evaluate the retention of the ECM paste within a gelatin tumor phantom after injection.

Materials and

Methods:  The primary materials used in this project are porcine extracellular matrix (ECM), phosphate buffered saline (PBS), sodium hyaluronate (SH), bovine collagen, and methylene blue dye. To achieve the first objective, various concentrations of each ingredient are added to a microcentrifuge tube and mixed thoroughly. A paste was noted as a solid material of a single phase that did not flow within a tube. Formulations that resulted in solutions, suspensions and pastes were recorded. The second objective involves determining an efficient method for loading paste formulas into syringes. Various techniques were tested, including backloading and aspiration. For the third objective, gelatin tumor phantoms were prepared by dissolving gelatin powder in water and in PBS and allowing it to set in molds to create tumor phantoms. After injecting several paste formulations into the tumor phantoms, the retention of the paste was assessed by visual inspection over several days.

Results, Conclusions, and Discussions: Pastes were formed with 3 to 50 milligrams of porcine ECM were added to 10 to 250 microliters of PBS. When too much PBS was added to the mixture, a two-phase suspension was formed. When creating a paste with just ECM and PBS, ratios between 3.25 and 13.25 microliters of PBS for every 10 mg of ECM were successful Other pastes were formed by combining 3 to 80 milligrams of ECM, 10 to 40 milligrams of SH, and 10 to 800 microliters of PBS. The addition of SH expanded the range of injectable pastes. The use of collagen as an alternative to ECM was also explored, with 10 to 70 milligrams of collagen and 0 to 35 milligrams of SH combined with 100 microliters of PBS being tested. With collagen and PBS pastes, ratios between 40 and 70 milligrams of ECM for every 100 microliters of PBS proved successful. All ECM and collagen pastes were able to be loaded into a syringe using a backloading technique. All ECM pastes were found to be injectable through a 21 gauge needle, though the force required to inject the paste was significantly greater at higher ratios of ECM to PBS (figure 1a). Collagen pastes were not injectable as they were too chunky. Upon injection into a gelatin tumor phantom, ECM pastes were retained (Figure 1b). Contrastingly, saline-based injections rapidly leaked from the tumor phantom. In conclusion, ECM pastes appear to be a promising delivery vehicle for localization of immunotherapies and other biologics.

Acknowledgements (Optional):  Thank you to the Freytes REdesign lab for supplying porcine ECM. This work was funded in part by the Office of Undergraduate Research at NC State.