Abstract No. 430 Self-assembling hydrogel platform improves intratumoral drug delivery and retention

Abstract

Direct intratumoral (IT) delivery of immunotherapeutics is an increasingly important intersection between interventional radiology and oncology. However, the challenge of IT drug deposition and retention has become apparent as drugs delivered in low viscosity fluids localize poorly in solid tumors. We hypothesized that drugs embedded in a multidomain peptide (MDP) hydrogel would exhibit significantly improved delivery and retention within tumors following percutaneous delivery. The cationic lysine-based MDP K2 (SL)6K2 (or K2-MDP) was used to load and test the biodistribution of the contrast agent iohexol. The radio-opacity of various hydrogel formulations containing 24, 48, and 120 mgI/mL iohexol and 1% wtK2-MDP stock peptide prepared in a buffered solution were tested via CT. Next, we generated a tumor model by subcutaneously implanting 5x106 McA-7777 cells in the 2 flanks of female Buffalo rats (n = 10). Once the tumors reached 1 cm in diameter, the MDP-iohexol hydrogel was injected using a 29G needle at a rate of 50 uL/sec under fluoroscopy, followed by immediate post injection CT scan. Injections of free iohexol in the contralateral tumors were used as controls. All formulations tested here were fully homogeneous and successfully formed hydrogels. The radio-opacity intensity curve showed that the optimal concentration for in vivo experiments was 60 mgI/mL within 1% wt K2-MDP. Fluoroscopic imaging during in vivo injection of free iohexol demonstrated leakage along the tumor capsule as well as venous intravasation. In marked contrast, there was substantially improved localization of the MDP-iohexol hydrogel within the tumor without intravasation. This was confirmed by subsequent CT imaging which demonstrated an approximately 5-fold improvement in the percentage of tumor volume containing the agent (38% vs. 8%, P < 0.001). Our K2-MDP hydrogel significantly improve intratumoral delivery of iohexol, suggesting that embedding immunotherapeutics in this hydrogel has the potential to improve the delivery and outcome in patients receiving intratumoral immunotherapy.