Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy

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  • March 19, 2019
Creator
  • Bloomquist, Cameron
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics
Abstract
  • With increasing interest in patient-specific dosage forms to tailor treatment and improve patient compliance, 3D printed drug formulations and medical devices have garnered much attention. The software-driven design and ability to fabricate a unique part with each print, makes 3D printing a versatile platform. This versatility affords personalization through anatomically-specific designs and the tuning a dosage form to each individual patient’s clinical needs. The recent introduction of the 3D printing technique, Continuous Liquid Interface Production (CLIP), presents a platform capable of producing devices in a rapid manner with mechanical properties suitable to serve as a final product rather than just a prototype. The study described herein is the investigation of CLIP as a methodology to fabricate drug-loaded, biocompatible medical devices with controlled release properties. We sought to characterize how parameters including crosslink density, polymer network composition, and the geometric complexity afforded by CLIP can be utilized to modify drug release from 3D printed dosage forms. Through systematic variation of the crosslink density and polymer composition of polycaprolactone and poly(ethylene glycol) based formulations, it was demonstrated that release kinetics of a small molecule drug surrogate, rhodamine B-base, can be modified through alterations in the resin formulation. Further, using a constant resin formulation, the RhB release was shown to be controllable through the geometric complexity built into the computer aided design (CAD) model. The suitability of CLIP for production of drug-loaded devices was investigated by screening a panel of clinically-relevant small molecule therapeutics for stability towards potential stresses from the CLIP process, including UV irradiation and interactions with free radicals. Additionally, select formulations were chosen to produce model devices which were tested for biocompatibility, degradation and encapsulation of a chemotherapeutic, docetaxel, and a corticosteroid, dexamethasone-acetate. Devices indicated biocompatibility over the course of 175 days of in vitro degradation and mirrored the release kinetics observed for the RhB model drug. Finally, these lessons learned were applied to the development and in vivo testing of two chemotherapeutic-loaded implantable devices: 1) an intraoperative implant for the prevention of lung cancer recurrence following resection and 2) brachytherapy spacers for the treatment of localized prostate cancer.
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Rights statement
  • In Copyright
Advisor
  • DeSimone, Joseph M.
  • You, Wei
  • Tepper, Joel
  • Lai, Samuel
  • Wang, Andrew
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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