Formulation Design and In Vitro/In Vivo Characterization of Anticancer Drug Delivery Systems
Digital Document
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http://hdl.handle.net/11134/20002:860653493
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Persons
Creator (cre): Suh, Min S.
Major Advisor (mja): Burgess, Diane J.
Associate Advisor (asa): Papadimitrakopoulos, Fotios
Associate Advisor (asa): Lu, Xiuling
Associate Advisor (asa): Kastellorizios, Michail
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Title |
Title
Title
Formulation Design and In Vitro/In Vivo Characterization of Anticancer Drug Delivery Systems
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Origin Information
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Parent Item
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Resource Type
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Digital Origin |
Digital Origin
born digital
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Description |
Description
The present dissertation focuses on formulation design of and in vitro/in vivo characterization of anticancer drug delivery systems for metastatic cancer treatment. There are two aspects to this work: i) formulation design and development of a nanoparticle platform for chemotherapy; and ii) characterization of in situ forming implants for hormone cancer therapy. The main goal of the first aim is to overcome side effects of chemotherapy that are significant concerns in the use of anticancer drugs through cancer active targeting and controlled drug release. A nanoparticle platform equipped with active targeting and pH-responsive functionalities was engineered using biocompatible materials with simple preparation methods, which may facilitate the development of nanoparticle drug products for cancer therapy. Nanoparticle uptake, therapeutic efficacy, and cytotoxicity were investigated using metastatic cancer cell models to evaluate anticancer performance of the nanoparticles. The main goal of the second aim is to identify critical factors affecting drug release kinetics of an in situ forming implant formulation. In vitro/in vivo characterization of in situ forming implants were investigated to understand implant formation and drug release mechanism. The characterization demonstrated that implant formation significantly impacts on drug release kinetics of ISFI formulations. A dissolution device was designed and created using 3D printing to generate biorelevant and reproducible drug release profiles of ISFIs. Water-dissolvable PVA films were combined with open window shaped 3D printed devices. This design allows implant formation without exposure to sink conditions. The results demonstrated that the 3D printed devices not only maintain consistent shape and size of ISFI formulations, but also generate reproducible in vitro release profiles. The 3D printed dissolution devices may prove a useful tool bioequivalence studies of ISFI formulations. Moreover, this work reports the first morphological and microstructural demonstration of in situ forming PLGA implants in a rabbit model.
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Genre
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Organizations
Degree granting institution (dgg): University of Connecticut
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Rights Statement
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Use and Reproduction |
Use and Reproduction
These materials are provided for educational and research purposes only.
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Local Identifier |
Local Identifier
OC_d_1743
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