TY - JOUR
T1 - Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins
AU - Bloomquist, Cameron J.
AU - Mecham, Michael B.
AU - Paradzinsky, Mark D.
AU - Janusziewicz, Rima
AU - Warner, Samuel B.
AU - Luft, J. Christopher
AU - Mecham, Sue J.
AU - Wang, Andrew Z.
AU - DeSimone, Joseph M.
N1 - Funding Information:
The authors would like to thank Carbon, Inc. for supporting this research. The authors would like to thank Dr. Ali Nebipasagil, Dr. Robert Pinschmidt, Dr. Zach Rodgers, Dr. Kevin Olson, and Dr. Adam Quintanilla for scientific discussions. This work was performed in part at the Chapel Hill Analytical and Nanofabrication Laboratory, CHANL, a member of the North Carolina Research Triangle Nanotechnology Network, RTNN, which is supported by the National Science Foundation, Grant ECCS-1542015, as part of the National Nanotechnology Coordinated Infrastructure, NNCI. A.Z.W is supported by National Institutes of Health/National Cancer Institute U54CA198999, R01 CA178748 and Department of Defense Congressionally Directed Medical Research Programs-Peer Reviewed Cancer Research Program Idea Award CA150391. Conflict of interest statement: J.M.D. has an equity stake in Carbon, Inc., which is a venture-backed manufacturer of continuous liquid interface production equipment. Continuous liquid interface production is the subject of patent protection including issued US patents 9,205,601, 9,211,678, and 9,216,546.
Publisher Copyright:
© 2018
PY - 2018/5/28
Y1 - 2018/5/28
N2 - Mass customization along with the ability to generate designs using medical imaging data makes 3D printing an attractive method for the fabrication of patient-tailored drug and medical devices. Herein we describe the application of Continuous Liquid Interface Production (CLIP) as a method to fabricate biocompatible and drug-loaded devices with controlled release properties, using liquid resins containing active pharmaceutical ingredients (API). In this work, we characterize how the release kinetics of a model small molecule, rhodamine B-base (RhB), are affected by device geometry, network crosslink density, and the polymer composition of polycaprolactone- and poly (ethylene glycol)-based networks. To demonstrate the applicability of using API-loaded liquid resins with CLIP, the UV stability was evaluated for a panel of clinically-relevant small molecule drugs. Finally, select formulations were tested for biocompatibility, degradation and encapsulation of docetaxel (DTXL) and dexamethasone-acetate (DexAc). Formulations were shown to be biocompatible over the course of 175 days of in vitro degradation and the clinically-relevant drugs could be encapsulated and released in a controlled fashion. This study reveals the potential of the CLIP manufacturing platform to serve as a method for the fabrication of patient-specific medical and drug-delivery devices for personalized medicine.
AB - Mass customization along with the ability to generate designs using medical imaging data makes 3D printing an attractive method for the fabrication of patient-tailored drug and medical devices. Herein we describe the application of Continuous Liquid Interface Production (CLIP) as a method to fabricate biocompatible and drug-loaded devices with controlled release properties, using liquid resins containing active pharmaceutical ingredients (API). In this work, we characterize how the release kinetics of a model small molecule, rhodamine B-base (RhB), are affected by device geometry, network crosslink density, and the polymer composition of polycaprolactone- and poly (ethylene glycol)-based networks. To demonstrate the applicability of using API-loaded liquid resins with CLIP, the UV stability was evaluated for a panel of clinically-relevant small molecule drugs. Finally, select formulations were tested for biocompatibility, degradation and encapsulation of docetaxel (DTXL) and dexamethasone-acetate (DexAc). Formulations were shown to be biocompatible over the course of 175 days of in vitro degradation and the clinically-relevant drugs could be encapsulated and released in a controlled fashion. This study reveals the potential of the CLIP manufacturing platform to serve as a method for the fabrication of patient-specific medical and drug-delivery devices for personalized medicine.
KW - 3D printing
KW - Additive manufacturing
KW - Continuous Liquid Interface Production
KW - Crosslink density
KW - Drug delivery
KW - Medical device
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U2 - 10.1016/j.jconrel.2018.03.026
DO - 10.1016/j.jconrel.2018.03.026
M3 - Article
C2 - 29596874
AN - SCOPUS:85044585514
SN - 0168-3659
VL - 278
SP - 9
EP - 23
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -