Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins

Cameron J Bloomquist; Michael B Mecham; Mark D Paradzinsky; Rima Janusziewicz; Samuel B Warner; J Christopher Luft; Sue J Mecham; Andrew Z Wang; Joseph M DeSimone

doi:10.1016/j.jconrel.2018.03.026

Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins

J Control Release. 2018 May 28:278:9-23. doi: 10.1016/j.jconrel.2018.03.026. Epub 2018 Mar 27.

Authors

Cameron J Bloomquist¹, Michael B Mecham², Mark D Paradzinsky², Rima Janusziewicz³, Samuel B Warner⁴, J Christopher Luft⁵, Sue J Mecham², Andrew Z Wang⁶, Joseph M DeSimone⁷

Affiliations

¹ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Lineberger Comprehensive Cancer Center Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27599, USA.
⁵ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁶ Lineberger Comprehensive Cancer Center Institute for 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, NC 27599, USA.
⁷ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center Institute for 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; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27599, USA; Department of Chemical and Biomedical Engineering, North Carolina State University, Raleigh, NC 27695, USA; Carbon, Redwood City, CA 94063, USA. Electronic address: desimone@unc.edu.

PMID: 29596874
DOI: 10.1016/j.jconrel.2018.03.026

Abstract

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.

Keywords: 3D printing; Additive manufacturing; Continuous Liquid Interface Production; Crosslink density; Drug delivery; Medical device.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Chemistry, Pharmaceutical / methods
Delayed-Action Preparations
Dexamethasone / administration & dosage
Dexamethasone / analogs & derivatives
Dexamethasone / chemistry
Docetaxel / administration & dosage
Docetaxel / chemistry
Drug Carriers / chemistry*
Drug Delivery Systems*
Drug Liberation
Polyesters / chemistry
Polyethylene Glycols / chemistry
Precision Medicine / methods
Printing, Three-Dimensional*
Rhodamines / administration & dosage
Rhodamines / chemistry
Technology, Pharmaceutical / methods*
Time Factors

Substances

Delayed-Action Preparations
Drug Carriers
Polyesters
Rhodamines
Docetaxel
polycaprolactone
Polyethylene Glycols
Dexamethasone
dexamethasone acetate
rhodamine B

Abstract

Publication types

MeSH terms

Substances

Grants and funding