4.8 Article

3D printed drug-loaded implantable devices for intraoperative treatment of cancer

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 344, Issue -, Pages 147-156

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2022.02.024

Keywords

3D printing; Continuous liquid interface production; Digital light synthesis; Personalized medicine; Drug-loaded device; Intraoperative chemotherapy; Cancer

Funding

  1. National Institutes of Health/National Cancer Institute [U54CA198999]
  2. National Institutes of Health [R01 EB25651]
  3. National Institute of Health Medical Scientist Training Program [T32 GM008719]
  4. Cancer Center Core Support Grant [P30 CA016086]
  5. [R01GM130590]

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This study utilized advances in 3D printing and drug delivery science to design a novel drug-loaded arrowhead array device (AAD) for localized chemotherapy at the surgical site, aiming to reduce local recurrence of cancer. The results demonstrated that the AAD significantly decreased local recurrence and improved survival in mouse cancer models, and showed potential for personalized treatment in the clinical setting.
Surgery is an important treatment for cancer; however, local recurrence following macroscopically-complete resection is common and a significant cause of morbidity and mortality. Systemic chemotherapy is often employed as an adjuvant therapy to prevent recurrence of residual disease, but has limited efficacy due to poor penetration and dose-limiting off-target toxicities. Selective delivery of chemotherapeutics to the surgical bed may eliminate residual tumor cells while avoiding systemic toxicity. While this is challenging for traditional drug delivery technologies, we utilized advances in 3D printing and drug delivery science to engineer a drug-loaded arrowhead array device (AAD) to overcome these challenges. We demonstrated that such a device can be designed, fabricated, and implanted intraoperatively and provide extended release of chemotherapeutics directly to the resection area. Using paclitaxel and cisplatin as model drugs and murine models of cancer, we showed AADs significantly decreased local recurrence post-surgery and improved survival. We further demonstrated the potential for fabricating personalized AADs for intraoperative application in the clinical setting.

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