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

C Tilden Hagan 4th; Cameron Bloomquist; Samuel Warner; Nicole M Knape; Isaiah Kim; Hayley Foley; Kyle T Wagner; Sue Mecham; Joseph DeSimone; Andrew Z Wang

doi:10.1016/j.jconrel.2022.02.024

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

J Control Release. 2022 Apr:344:147-156. doi: 10.1016/j.jconrel.2022.02.024. Epub 2022 Feb 22.

Authors

Affiliations

¹ Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill/North Carolina State University, Chapel Hill, NC 27599, USA.
² Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁶ Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Chemical Engineering, Stanford University School of Engineering, Stanford, CA 94305, USA; Carbon, Inc, Redwood City, CA 94063, USA. Electronic address: jmdesimone@stanford.edu.
⁷ Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: andrew.wang2@utsouthwestern.edu.

Abstract

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.

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

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Drug Delivery Systems*
Mice
Neoplasms* / drug therapy
Paclitaxel
Pharmaceutical Preparations
Printing, Three-Dimensional

Substances

Pharmaceutical Preparations
Paclitaxel

Abstract

Publication types

MeSH terms

Substances

Grants and funding