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Yewon Joanna Pak Email In-vitro Efficacy and Intracellular Mechanism of Riboflavin- Conjugated PEGylated Poly- L-Lysine Dendrimer Item Type dissertation Authors Pak, Yewon Publication Date 2017 Abstract Chemotherapeutic drugs have advanced using different drug delivery methods to treat breast cancer specifically. This development has arisen because many classical drugs exhibit physicochemical limitations including solubility, specificity, stability,... Keywords Dendrimers; Doxorubicin; Drug Delivery Systems; Riboflavin Download date 24/09/2021 01:49:54 Link to Item http://hdl.handle.net/10713/7049 Curriculum Vitae Contact Information: Yewon Joanna Pak Email: [email protected] Education Ph.D Candidate in Pharmaceutical Sciences, Aug 2011-July 2017 University of Maryland-Baltimore, Baltimore, MD Bachelor of Sciences in Chemistry and Bachelor of Arts in Biochemistry, September 2006-June 2011 University of Washington, Seattle, WA Research Experience Graduate Research Assistant (Ph.D Candidate), August 2011-July 2017 University of Maryland, Baltimore, Department of Pharmaceutical Sciences Advisor: Dr. Peter W. Swaan, Ph.D Investigated synthesizing and formulating a nanoparticle/polymer drug delivery system, dendrimer, with a drug compound to efficiently deliver the drug to its targeting tumor cells. Undergraduate Research Lab Assistant, February 2010-June2011 University of Washington, Department of Pharmaceutics Investigated functional characterization of mouse PMAT (Plasma Membrane Monoamine Transporter). Experimented with mouse PMAT on transport uptake of certain radioactive compounds like MPP+, Dopamine, and 5-HT. Student Assistant, July2007-April 2008 University of Washington, Department of Chemistry, Center on Materials and Devices for Information Technology Research Daily works including filings, using Excel, and handling projects. Other jobs consisted of preparing for conference by making pamphlets, sending out mails and organizing the website. Helped organizing conference preparations including Friday Harbor Conference 2007 and Retreat/Expo Survey 2007. Lab Assistant, April 2008-June 2008 University of Washington, Department of Environmental Science Filtered urine for eliminating substances that was not needed, cleaned instruments, and managed certain bottles of urine by separating them. Skills Acquired Cell culture, Calorimetric Assays, Atomic Microscopy, Mass Spectrometry, Chromatography- analytical HPLC, UPLC, Size Exclusion Chromatography (SEC), Reverse Phase Chromatography, Liquid chromatography–mass spectrometry (LC-MS), Confocal microscopy imaging, Inverted microscpy imaging, UV-Vis Spectroscopy, Fluorescence Anisotropy, Zetasizer/DLS, Cytotoxicity assays, Purification methods, antibody staining, and Pharmacokinetic modeling with Pharsight (NONMEM and WinNonlin). Leadership and Activities American Association of Pharmaceutical Scientist (AAPS) Student Chapter Secretary, October 2014-October 2015 University of Maryland, Baltimore Responsibilities include writing minutes during chapter meetings, and organizing AAPS student chapter events including seminars. Have worked diligently and proficiently in dynamic team settings with people from different research background. American Association of Pharmaceutical Scientist (AAPS) Student Chapter Treasurer, September 2012-October 2014 University of Maryland, Baltimore Demonstrated interpersonal skills by recruiting speakers from different places and interacting with researchers. Responsibilities included managing AAPS student account, filing expenses, and organizing AAPS student chapter events including seminars. Research Translator, September 2013-September 2014 Heajin Jung Law Firm LLC: Life Science Tech Transfer Translated research papers from Korean to English. Also, translated and made brochures and presentationsfor different pharmaceutical companies. President's Leadership Student Institute (PSLI), September 2012-May 2013 University of Maryland, Baltimore Participated in attending different leadership seminars and volunteered for more than 20 hours to help Baltimore community. US-Korea Conference on Science, Technology, and Entrepreneurship (UKC) Conference 2010 volunteer, August 2010 Korean-American Scientists and Engineers Association (KSEA) Took notes on the speakers from different areas of study including pharmaceutical science and chemistry. Also, participated in organizing registration, and assisted with events during the conference. Honors and Award Rho Chi Honors Society, University of Maryland-Baltimore, February 2016- August 2017 Dr Gerald P and Margaret M Polli Graduate Student Travel Awards, October 2015 CBI Training Grant, July 2014-July 2016 USA Funds Access to Education Scholar, September 2006-June 2010 Special Programs and Certifications Chemistry and Biology Interface Program NIH supported program, which prepared students to pursue cross-disciplinary training in the chemical and biological sciences. Includes presenting a seminar in front of peers two times a year and participating in research at another discipline. Tablets & Capsules Short Course Participated in lectures and hands-on laboratory sessions for learning process of formulation and manufacturing multi-particulate beads, capsules and tablets. Abstracts/ Poster Presentations Yewon Pak and P. Swaan. "Anti-Cancer Efficacy of PEGylated Poly-L-Lysine Dendrimer with Doxorubicin." Annual Nanomedicine and Drug Delivery Symposium. September 15, 2015. Baltimore, MD. Y. J. Pak and P. Swaan. "Synthesis and Characterization of Native and PEGylated Poly-L-Lysine Dendrimers." Graduate Research Conference. March 23, 2016. Baltimore, MD. Y. J. Pak and P. Swaan. "Synthesis and Characterization of Native and PEGylated Poly-L-Lysine Dendrimers." American Association of Pharmaceutical Scientists Annual Conference 2015. October 25, 2015. Orlando, FL. Y. J. Pak and P. Swaan. "Synthesis and Characterization of Native and PEGylated Poly-L-Lysine Dendrimers." Globalization of Pharmaceutics Education Network Conference 2014. August 28, 2014. Helsinki, Finland. Publications Y. J. Pak*, B. Avaritt*, P. Swaan. “Dendrimers: Origins, Architectures, and Applications” Journal of Pharmaceutical Research, Submitted on July 6, 2017 Y.Shirasaka, N. Lee, H. Duan, and J Pak.“Interspecies Comparison of the Functional Characteristics of Plasma Membrane Monoamine Transporter (PMAT) between Human, Rat and Mouse. “ Journal of Chemical Neuroanatomy. Accepted 14 Sept. 2016. Y. J. Pak, P. Swaan.“In-vitro Efficacy of Riboflavin Conjugated PEGylated Poly-L- Lysine Dendrimer” in preparation for submission Y. J. Pak, P. Swaan.“Intracellular Trafficking of Riboflavin Conjugated PEGylated Poly-L-Lysine Dendrimer” in preparation for submission Abstract Title of Dissertation: In-vitro Efficacy and Intracellular Mechanism of Riboflavin- conjugated PEGylated Poly-L-Lysine Dendrimer Yewon Joanna Pak, Doctor of Philosophy, 2017 Dissertation Directed by: Peter Swaan, Ph.D. Associate Dean for Research and Graduate Education Director of the Center for Nanobiotechnology Department of Pharmaceutical Sciences School of Pharmacy University of Maryland, Baltimore, MD, USA Chemotherapeutic drugshave advanced using different drug delivery methodsto treat breast cancer specifically. This development has arisen because many classical drugs exhibit physicochemical limitations including solubility, specificity, stability, biodistribution, and therapeutic efficacy. There were numerous adverse effectsassociated with these limitations because chemotherapeutic drugs enter normal tissues. In order to eliminate off-target side effect, nanoparticles were developed to target anticancer drugs to a specific carcinogenic area. As one of developing nanomedicines, dendrimers possess ability to be utilized in different administration routes and has potential to stay in the blood circulation longer while showing increased accumulation in tumor cells. Commercially available poly (amidoamine) (PAMAM) dendrimers have the potential to cause toxicity in-vivodue to lack of biodegradation at sites of accumulation. Poly-L-Lysine (PLL) dendrimers are an alternative class of dendrimers that possess a biodegradable structure. PEGylated poly-l-lysine (PLL) dendrimers are known to be more favorable due to lessened cytotoxicity manifested by masking of cationic charges and avoiding uptake by Reticulo Endothelial System (RES). Using this biodegradable dendrimer, we sought to examine the effect of PEGylation as well as delivering anti-cancer drug, Doxorubicin (DOX), to a targeted internalization pathway in human breast cancercells effectively. PEGylated PLL dendrimers also have their limitation, in which some tumor cells are not dependent upon enhanced permeability and retention (EPR) effect. As a result, riboflavin receptor, which is found to be upregulated in the exterior of breast and ovarian cancer cells, was utilized by attaching a riboflavin ligand to PEGylated PLL dendrimers in order to be actively uptaken by breast cancer cells. To target chemotherapeutic drug selectively and efficaciously, riboflavin (RF) conjugated PLL dendrimers were assessed in-vitro by investigating cytotoxicity, uptake accumulation, and intracellular colocalization. Further investigation on the endocytosis mechanism and detailed intracellular trafficking in different compartments of the cells were analyzed in order to fully understand the machinery behind delivering chemotherapeutic drugs successfully. In-vitro Efficacy and Intracellular Mechanism of Riboflavin-conjugated PEGylated Poly-L-Lysine Dendrimer by Yewon Joanna Pak Dissertation
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