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Nanoparticles Using Static Mixers University of Kentucky UKnowledge University of Kentucky Master's Theses Graduate School 2008 PROCESS FOR FORMATION OF CATIONIC POLY (LACTIC-CO- GLYCOLIC ACID) NANOPARTICLES USING STATIC MIXERS Yamuna Reddy Charabudla University of Kentucky Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Charabudla, Yamuna Reddy, "PROCESS FOR FORMATION OF CATIONIC POLY (LACTIC-CO-GLYCOLIC ACID) NANOPARTICLES USING STATIC MIXERS" (2008). University of Kentucky Master's Theses. 580. https://uknowledge.uky.edu/gradschool_theses/580 This Thesis is brought to you for free and open access by the Graduate School at UKnowledge. It has been accepted for inclusion in University of Kentucky Master's Theses by an authorized administrator of UKnowledge. For more information, please contact [email protected]. ABSTRACT OF THESIS PROCESS FOR FORMATION OF CATIONIC POLY (LACTIC-CO-GLYCOLIC ACID) NANOPARTICLES USING STATIC MIXERS Nanoparticles have received special attention over past few years as potential drug carriers for proteins/peptides and genes. Biodegradable polymeric poly (lactic-co-glycolic acid) (PLGA) nanoparticles are being employed as non-viral gene delivery systems for DNA. This work demonstrates a scalable technology for synthesis of nanoparticles capable of gene delivery. Cationic PLGA nanoparticles are produced by emulsion- diffusion-evaporation technique employing polyvinyl alcohol (PVA) as stabilizer and chitosan chloride for surface modification. A sonicator is used for the emulsion step and a static mixer is used for dilution in the diffusion step of the synthesis. A static mixer is considered ideal for the synthesis of PLGA nanoparticles as it is easily scalable to industrial production. The resulting nanoparticles are spherical in shape with size in the range of 100–250 nm and posses a zeta potential above +30 mV, indicating good stability of the colloid with a positive charge to bind to anionic DNA. The mechanism of nanoparticle formation was analyzed using multimodal size distributions (MSD), zeta potential data, and transmission electron microscopy (TEM) images. Several emulsion techniques and dilution effect were analyzed in this work. PVA acts as a compatibilizer for chitosan chloride and dilution of primary emulsion has little effect over the particle size of the PLGA nanoparticles. Key Words: Emulsion solvent diffusion technique, Nanoparticles, PLGA, Static mixer, Chitosan. Yamuna Reddy Charabudla 08-14-2008 PROCESS FOR FORMATION OF CATIONIC POLY (LACTIC-CO-GLYCOLIC ACID) NANOPARTICLES USING STATIC MIXERS By YAMUNA REDDY CHARABUDLA Dr. Eric A. Grulke Director of Thesis Dr. Douglass S. Kalika Director of Graduate Studies 01-05-2008 Date RULES FOR THE USE OF THESES Unpublished theses submitted for the Master’s degree and deposited in the University of Kentucky Library are as a rule open for inspection, but are to be used only with due regard to the rights of the authors. Bibliographical references may be noted, but quotations or summaries of parts may be published only with the permission of the author, and with the usual scholarly acknowledgments. Extensive copying or publication of the thesis in whole or in part also requires the consent of the Dean of the Graduate School of the University of Kentucky. THESIS Yamuna Reddy Charabudla The Graduate School University of Kentucky 2009 PROCESS FOR FORMATION OF CATIONIC POLY (LACTIC-CO-GLYCOLIC ACID) NANOPARTICLES USING STATIC MIXERS THESIS A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Chemical Engineering in the College of Engineering at the University of Kentucky By Yamuna Reddy Charabudla Lexington, Kentucky Director: Dr. Eric A. Grulke, Professor of Chemical and Materials Engineering Lexington, Kentucky 2009 ACKNOWLEDGEMENTS I would like to thank my adviser, Dr. Eric A. Grulke for giving me the opportunity to work on such wonderful project. This work would not have been possible without his constant support and guidance. I would like to thank my thesis committee members: Dr. Tate T.H. Tsang and Dr. Stephen E. Rankin for their valuable inputs that helped me deliver a better finished product. I am thankful to my friends and family for believing in me and for extending their constant support. iii TABLE OF CONTENTS Acknwledgements .............................................................................................................. iii List of Tables ..................................................................................................................... vi List of Figures ................................................................................................................... vii List of Files ...................................................................................................................... xiv 1. Introduction ..................................................................................................................1 2. Literature Review .........................................................................................................2 Drug delivery and drug delivery systems .........................................................................2 Gene delivery ...................................................................................................................3 Nanoparticles and physicochemical properties ................................................................4 Polymeric nanoparticles and polymer selection for synthesis .........................................6 Synthesis of polymeric nanoparticles ...............................................................................9 PLGA, PVA and chitosan chloride ................................................................................12 Static Mixers ..................................................................................................................14 3. Materials and methods ................................................................................................16 Materials .........................................................................................................................16 Sonication .......................................................................................................................16 Colloid Mixer .................................................................................................................16 Static mixer ....................................................................................................................17 Characterization of nanoparticles ...................................................................................18 Light scattering particle size analysis .........................................................................18 Zeta potential Measurements ......................................................................................19 Transmission electron microscope (TEM) analysis ...................................................19 4. Results and discussion ................................................................................................20 Mechanisms for formation of nanoparticles ...................................................................20 Dissolution of polymers in their solvents ...................................................................20 Different possible binary polymer emulsions .............................................................25 iv Emulsion formed by the ternary polymer system .......................................................36 Synthesis of cationic PLGA nanoparticles .....................................................................40 Preliminary work ........................................................................................................40 Effect of static mixer on size of nanoparticles ...........................................................40 Sonication and Homogenization .................................................................................46 Dilution effect on the size of the particles ..................................................................51 Sonication and Static mixer ........................................................................................56 Transmission electron microscopy measurement ..........................................................62 5. Conclusions ................................................................................................................68 6. Appendices .................................................................................................................69 Abbreviations .................................................................................................................69 Polymers .....................................................................................................................69 Nomenclature ..............................................................................................................69 Number based multimodal size distributions of all secondary emulsions in this work .70 Dissolution of polymers in their solvents (Table 4.1) ................................................70 Effect of PVA on Chitosan chloride aqueous solution (Table 4.2) ............................71 Different possible binary polymer emulsions (Table 4.3) ..........................................74 Emulsion formed by the ternary polymer system (Table 4.4) ....................................76 Effect of Static
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