Background: Surgery is a key treatment for cancer. However, local recurrence after surgery is common and can lead to significant morbidity and mortality. Current strategies to prevent recurrence include intraoperative… Click to show full abstract
Background: Surgery is a key treatment for cancer. However, local recurrence after surgery is common and can lead to significant morbidity and mortality. Current strategies to prevent recurrence include intraoperative radiation or systemic chemotherapy. We hypothesize that local chemotherapy delivery can prevent recurrence while reducing toxicity. To accomplish this, we propose to engineer 3D printed devices that can deliver chemotherapy in a localized and prolonged fashion. Methods: Paclitaxel and a cisplatin prodrug were dissolved into a liquid resin mixture of PEG550-DMA and HEMA. Custom 3D patches were printed on a Carbon 3D continuous liquid interface printer with microneedles protruding from one side of a flat surface substrate. A non-drug loaded flat backing was also printed from the same resin, and adhered to back side of the microneedle patch. Tumor growth recurrence inhibition post surgical resection was assessed in NU/NU mice in both 344SQ/Luc and A431 tumor models. Tumors were inoculated subcutaneously (106 344SQ/Luc, 5 × 105 A431) and allowed to grow until they reached 5-7mm in length. Tumors were then surgically resected and mice were either given an IV drug treatment, or had a 3D printed patch implanted in the surgical pocket. Tumor recurrence was evaluated with both luciferase bioluminescence imaging and physical measurement of tumor size. Toxicity parameters were analyzed with enzyme and CBC tests. Results: All drug loaded patches showed significant tumor growth inhibition compared to their corresponding IV drug treatment groups. While single drug loaded patches were significant in their inhibition of tumor growth compared to IV delivery of the same drug, dual drug loaded patches showed the most significant tumor inhibition compared to either single IV drug treatment or a dual IV drug treatment. There were no significant differences in measured toxicity parameters between groups. Conclusions: Our data demonstrated that local drug delivery through a customizable 3D continuous liquid interface printed drug loaded patch can improve tumor growth recurrence inhibition post surgical resection. Citation Format: C. Tilden Hagan, Cameron J. Bloomquist, Joseph M. DeSimone, Andrew Z. Wang. Drug delivery with real time customizable micro-scaled continuous liquid interface printed 3D devices [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6247.
               
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