ingest cdrApp 2018-03-15T17:05:31.885Z d591f2cd-3da7-4b31-9dd8-ee27dcb6a3ee modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-03-15T17:06:24.467Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2018-03-15T17:06:35.674Z Adding technical metadata derived by FITS addDatastream MD_FULL_TEXT fedoraAdmin 2018-03-15T17:06:59.179Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-03-15T17:07:21.384Z Setting exclusive relation modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-05-16T21:15:41.223Z Setting invalid vocabulary terms modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-05-16T21:15:52.620Z modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-05-30T18:27:30.313Z Setting invalid vocabulary terms modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-05-30T18:27:41.369Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-10T22:15:15.208Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-17T18:23:45.568Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-08T17:50:28.666Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-15T14:57:42.979Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-16T18:00:42.828Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-21T15:29:59.873Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-26T18:29:13.863Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-11T19:15:59.069Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-02-28T02:36:14.090Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-19T21:53:52.826Z Cameron Bloomquist Author Pharmaceutical Sciences Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. Winter 2017 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Pharmaceutical Sciences Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph M. DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation Pharmaceutical Sciences Joseph M. DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing; Additive manufacturing; Continuous Liquid Interface Production; Controlled release; drug delivery; medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing, Additive manufacturing, Continuous Liquid Interface Production, Controlled release, drug delivery, medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph M. DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing; Additive manufacturing; Continuous Liquid Interface Production; Controlled release; drug delivery; medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmaceutical Sciences Joseph M. DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Cameron Bloomquist Creator Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy Continuous Liquid Interface Production of Medical Devices for Drug Delivery and Cancer Therapy 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. 2017-12 2017 Pharmaceutical sciences Polymer chemistry Biomedical engineering 3D printing; Additive manufacturing; Continuous Liquid Interface Production; Controlled release; drug delivery; medical device eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Joseph M. DeSimone Thesis advisor Samuel Lai Thesis advisor Joel Tepper Thesis advisor Andrew Wang Thesis advisor Wei You Thesis advisor text Bloomquist_unc_0153D_17379.pdf uuid:afee505c-213f-4bff-b7d7-bed6e5d30e6b 2017-10-26T15:40:32Z proquest 2019-12-31T00:00:00 application/pdf 16355581