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