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Magnet-Directed Bioadhesive Nanoparticles for Localized Oral Delivery

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Magnet-Directed Bioadhesive Nanoparticles for Localized Oral Delivery Magnet-Directed Bioadhesive Nanoparticles for Localized Oral Delivery by Bryan Laulicht B.A. Columbia University, 2005 Submitted in partial fulfillment of the Requirements for the degree of Doctor of Philosophy In the Division of Biology and Medicine at Brown University Providence, Rhode Island May 2010 © Copyright 2010 by Bryan Laulicht This dissertation by Bryan Laulicht is accepted in its present form by the Division of Biology and Medicine as satisfying the dissertation requirement for the degree of Doctor of Philosophy. Date _______________ _________________________________ Edith Mathiowitz, Ph.D., Director Recommended to the Graduate Council Date _______________ _________________________________ Anubhav Tripathi, Ph.D., Co-Advior Date _______________ _________________________________ Diane Hoffman-Kim, Ph.D., Reader Date _______________ _________________________________ Jeffrey Morgan, Ph.D., Reader Date _______________ _________________________________ Solomon Steiner, Ph.D., External Reader Approved by the Graduate Council Date _______________ _________________________________ Sheila Bonde Dean of the Graduate School iii Curriculum Vitae Bryan Laulicht Date of Birth: August 26, 1981 Place of Birth: New York, NY EDUCATION Brown University, Providence, RI Expected May, 2010 PhD, Medical Science . Program in Artificial Organs, Biomaterials, and Cellular Technology, Department of Molecular Pharmacology, Physiology, and Biotechnology Advisors: Edith Mathiowitz, PhD and Anubhav Tripathi, PhD Thesis: Magnet-Directed Bioadhesive Nanoparticles for Localized Oral Delivery Columbia University, New York, NY May, 2005 BA, Biophysics. Isidor Isaac Rabi Science Research Scholar iv RESEARCH EXPERIENCES Perosphere Biopharmaceuticals , Providence, RI 2009-Present Optimize bioadhesive polymer nanosphere formulations to maximize uptake Formulate oral protein delivery systems Biodel Inc. , Providence, RI 2008-Present Analyze and optimize long-acting insulin formulations Brown University , Providence, RI 2005-Present Develop magnetically retentive drug delivery systems Characterize the safety of magnetically-retained pills in vivo using biplanar fluoroscopy Determine the effectiveness of magnetic retention in the small intestines in a small animal model Develop nanosphere formulations to improve uptake of narrow absorption window therapeutics (e.g. Lasix for congestive heart failure) Engineered Release Systems Inc. , Rensselaer, NY 2003-Present Develop bioinspired surgical materials Design and produce MEMS systems for single-cell microencapsulation HID International , Providence, RI 2008 Test the effects of mechanically induced birefringence on the mechanical properties of biodegradable smart cards v Freedom-2 Inc. , Providence, RI 2007-2008 Development of encapsulated inks for use in permanent removable tattoos Scale-up process to pilot scale Scale-up and manufacturing of dermal filler Center for Nanoscale Science and Engineering , Albany, NY 2004-2005 Collaborative Effort with Columbia University Microelectronics Sciences Lab to investigate the mechanism of implantation-based lift- off in Helium implanted Lithium Niobate thin films Columbia University , New York, NY 2002-2004 Investigate the mechanism of giant uni-lamellar vesicle formation Design and construct a high pressure nano-perfusion bioreactor for articular cartilage permeability testing Weizmann Institute of Science , Rehovot, Israel 1999 Synthesized siderophores for use as an antibiotic delivery system to combat drug resistant infections Michigan State University , East Lansing, MI 1998-9 Investigated the behavior of vortex rings propagating through tubes of varying diameters using laser induced fluorescence Cold Spring Harbor Laboratories , Cold Spring Harbor, NY 1996-8 Identified and genotypically characterized a female sterile mutant Arabidopsis thaliana that had been induced by DS tag insertion for the Arabidopsis Genome Project vi PUBLICATIONS 1. Bryan Laulicht, Anubhav Tripathi, Vincent Schlageter, Pavel Kucera, Edith Mathiowitz, “Understanding Gastric Forces Calculated from High Resolution Pill Tracking Data” PNAS April 19, 2010, 10.1073/pnas.1002292107. 2. Bryan Laulicht, Peter M. Cheifetz, Anubhav Tripathi, Edith Mathiowitz, “Are in vivo gastric bioadhesive forces accurately reflected by in vitro experiments?” Journal of Controlled Release 2009, 134(2), 103-110. 3. Bryan Laulicht, Peter Cheifetz, Edith Mathiowitz, Anubhav Tripathi, “Evaluation of Continuous Flow Nanosphere Formation by Controlled Microfluidic Transport,” Langmuir 2008, 24 (17), 9717-26. 4. Ryan M. Roth, Djordje Djukic, Yoo Seung Lee, Richard M. Osgood, Sasha Bakhru, Bryan Laulicht, Kathleen Dunn, Hassaram Bakhru, Liqi Wu, Mengbing Huang, “Compositional and structural changes in LiNbO3 following deep He+ ion implantation for film exfoliation,” Applied Physics Letters 2006, 89(11)112906,1-3. 5. Joshua Reineke, Yu-Ting Liu, Daniel Cho, A. Peter Morello III, Bryan Laulicht, Edith Mathiowitz, “Mechanisms of Polymer Microsphere Uptake Following Oral Delivery” in process. 6. Bryan Laulicht, Nicholas J Gidmark, Anubhav Tripathi, Edith Mathiowitz, “A New Method for Improving Localized Delivery from Magnetic Pills” in process. 7. Bryan Laulicht, Alexis Mancini, Nathanael Geman, Anubhav Tripathi, Edith Mathiowitz, “Bioinspired Synthetic Bioadhesive Polymers,” in process. vii 8. Bryan Laulicht, Anubhav Tripathi, Edith Mathiowitz, “Bioactivity Optimization of Furosemide Nanospheres” in process. 9. Peter M. Cheifetz, Sarah Rose, Elaine Kim, Jill Javier, Bryan E. Laulicht, Haitao Qian, Jules Jacob, Avinash Nangia, Anubhav Tripathi, Edith Mathiowitz, “Development of New Artificial Tissue Substrate for Bioadhesion Testing,” in process. PATENTS 1. Bryan Laulicht, Edith Mathiowitz. “Magnet-Retained Localized Oral Drug Delivery Systems,” invention disclosure submitted. 2. Edith Mathiowitz, Arthur Peter Morello, Joshua Reineke, Bryan Laulicht, Peter Cheifetz. “Drug Delivery Formulations for Targeted Delivery,” Patent application US2008193543 , WO2006125074, filed May 17, 2006. 3. Bryan Laulicht, Sasha Bakhru. “Chemically Cross-linked Elastomeric Microcapsules,” US2006/027163, WO/2007/009023. 4. Bryan Laulicht, Sasha Bakhru. “Polymer-Based Microstructures,” Patent application US2004/036158, WO/2005/041884, filed October 29, 2004. TEACHING EXPERIENCE Teaching Assistantships, Brown University Principles of Experimental Surgery Spring 2007 Biotechnology in Medicine Fall 2006 viii Invited Lectures, Brown University Bioadhesion, Drug and Gene Delivery Fall 2009 Co-Instructor of Drug and Gene Delivery with Professor Edith Mathiowitz Fall 2008 Bioadhesive and Bioerodible Drug Delivery, Polymer Science for Biomaterials Fall 2008 Graduate Education in the Biomedical Sciences, Introduction to Biotechnology Fall 2008 PRESENTATIONS/ABSTRACTS 1. Bryan Laulicht, Peter Cheifetz, Edith Mathiowitz, Anubhav Tripathi, “Are in vivo gastric bioadhesive forces accurately reflected by in vitro experiments?” Controlled Release Society Annual Meeting, Copenhagen, Denmark, July 18-22, 2009. 2. Bryan Laulicht, Peter Cheifetz, Edith Mathiowitz, Anubhav Tripathi, “Evaluation of Continuous Flow Nanosphere Formation by Controlled Microfluidic Transport,” AIChE Annual Meeting, Philadelphia, PA, November 16-21, 2008. 3. Cartney Smith, Peter Cheifetz, Bryan Laulicht, Edith Mathiowitz, Anubhav Tripathi, “Targeting Precise Nanoencapsulation by Controlled Microfluidic Transport,” Showcase of Nanomedicine, Providence, RI, May 24, 2006. 4. Bryan Laulicht, Doglas Bohl, Manoochehr Koochesfahani, “Vortex Ring in a Tube” American Physical Society Division of Fluid Dynamics Annual Meeting, Philadelphia, PA, November 22-4, 1998. ix RESEARCH AWARDS Columbia University Isidor Isaac Rabi Science Research Scholar 1999-2005 First Step to the Nobel Prize in Physics, Grand Prize Recipient 1999 Intel Science Talent Search Semifinalist 1999 International Science and Engineering Fair, 2 nd Place in Engineering 1999 University of Pennsylvania Roy and Diana Vagelos Scholar (declined) 1999 Hunter R. Rawlings III Cornell Presidential Research Scholar (declined) 1999 CONSULTING Franz Cell Optimization for Transdermal Drug Delivery, Isis Biopolymer Spring 2010 Characterization of Coated Microparticles, Panacos Pharmaceuticals Fall 2009 Cellulose-Derivative Gel Viscosity Determination, GelMed Sciences Fall 2008 PROFESSIONAL ASSOCIATIONS American Association for the Advancement of Science Controlled Release Society American Institute of Chemical Engineers Society for Bioengineers Sigma Xi x Acknowledgements I wish to express my deepest gratitude to my thesis advisors, Professors Edith Mathiowitz and Anubhav Tripathi, for their constant encouragement, invaluable guidance, and unending enthusiasm about our work. I also thank my thesis committee – Professors Diane Hoffman-Kim, Jeffrey Morgan, and Solomon Steiner – for their time and most helpful advice. I similarly extend heartfelt thanks to my collaborators and former labmates at Brown; their friendship and support made my graduate experience exciting and fruitful, and for this I will be forever grateful. In particular, I thank Dr. Peter Cheifetz for acclimating me to the Mathiowitz laboratory and for his collaborative efforts on characterizing bioadhesives and fabricating nanospheres. I also thank Dr. A. Peter Morello III for teaching me about polymer characterization and for all of his insightful and exciting discussions. I thank Professor Joshua Reineke for all of his work and discussions regarding the links
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