Pharmaceutical Nanotechnology Pharmaceutical Nanotechnology Development of Gold-Chitosan-coated PLGA Nanoparticles Marius Hittinger 28.04.2011 Supervisor: Juniorprofessor Dr. Marc Schneider Pharmaceutical Nanotechnology Gold Nanoparticles Advantages: -Easy to prepare -Special optical properties -Surface modifications possible -Stable -Biocompatible Haiss et al. 2007 Gold Nanoparticles Advantages: -Easy to prepare -Special optical properties -Surface modifications possible -Stable -Biocompatible Giljohann et al. 2010 PLGA-Chitosan Nanoparticles Advantages: -Easy to prepare -Biodegradable -Biocompatible Nafee et al. 2007 -High efficient drug delivery vehicle -Permeability-enhancing properties (chitosan) http://de.wikipedia.org/wiki/Polylactid-co-Glycolid http://de.wikipedia.org/wiki/Chitosan Multifunctional Nanoparticles Park et al. 2007 Multifunctional Nanoparticles Park et al. 2007 Multifunctional Nanoparticles Park et al. 2007 Turkevich - Method 1.! Synthesis 2.! Characterization 3.! Preparation of combined particles 4.! Characterization Kumar et al. Turkevich - Method (1951) Ojea-Jiménez et al. 2010 http://mrsec.wisc.edu/Edetc/nanolab/gold/index.html Turkevich - Method (1951) Ojea-Jiménez et al. 2010 http://mrsec.wisc.edu/Edetc/nanolab/gold/index.html Preparation of PLGA-Chitosan NPs Kumar et al. 2004 Turkevich - Method 1.! Synthesis 2.! Characterization 3.! Preparation of combined particles 4.! Characterization Kumar et al. Preparation - Basic ideas: -Calculate the maximum of particles which can take place on the surface and dilute gold solution before interaction (80%,15%,0%) -Use undiluted gold solution and separate new particles from the AuNP -solution (100%) Preparation - Basic ideas: -Calculate the maximum of particles which can take place on the surface and dilute gold solution before interaction (80%,15%,0%) -Use undiluted gold solution and separate new particles from the AuNP -solution (100%) Magnetic particles Filtration Centrifugation Turkevich - Method 1.! Synthesis 2.! Characterization 3.! Preparation of combined particles 4.! Characterization Kumar et al. Characterization - + + + ? TEM SEM AFM NanoSight Characterization IR - + + - ? ZetaSizer + UV/VIS CLSM What can I expect ? Preston et al. 2009 What can I expect ? Preston et al. 2009 What can I expect ? Kumar et al. 2004 Darwich et al. 2011 What could be possible ? Multifunctional PLGA-Chitosan-Gold-Nanoparticles What could be possible ? Multifunctional PLGA-Chitosan-Gold-Nanoparticles What could be possible ? -Alginate-Chitosan-Gold-Nanoparticles -Cellular uptake -Microparticles David A. Giljohann, Dwight S. Seferos, Weston L. Daniel, Matthew D. Massich, Pinal C. Patel, and Chad A. Mirkin: Gold Nanoparticles for Biology and Medicine Angew. Chem.(49) 3280 – 3294 2010 Spectra Wolfgang Haiss, Nguyen T. K. Thanh, Jenny Aveyard, and David G. Fernig: Determination of Size and Concentration of Gold Nanoparticles from UV-Vis Anal. Chem.(79) 4215-4221 2007 John Turkevich, Peter Cooper Stevenson and James Hillier: A study of the nucleation and growth processes in the synthesis of colloidal gold Discuss. Faraday Soc., 1951, 11, 55-75 Isaac Ojea-Jimnez, Francisco M. Romero, Neus G. Basts and Victor Puntes: Small Gold Nanoparticles Synthesized with Sodium Citrate and Heavy Water: Insights into the Reaction Mechanism J. Phys. Chem. C, 2010, 114 (4), pp 1800–1804 Samer Darwich1, Karine Mougin*1, Akshata Rao2, Enrico Gnecco2, Shrisudersan Jayaraman3 and Hamidou Haidara: Manipulation of gold colloidal nanoparticles with atomic force microscopy in dynamic mode: influence of particle–substrate chemistry and morphology, and of operating conditions Beilstein J. Nanotechnol. 2011, 2, 85–98 Noha Nafee,Sebastian Taetz, Marc Schneider, Ulrich F. Schaefer, Claus-Michael Lehr : Chitosan-coated PLGA nanoparticles for DNA/RNA delivery: effect of the formulation parameters on complexation and transfection of antisense oligonucleotides Nanomedicine: Nanotechnology, Biology, and Medicine (3) 173–183 2007 LayerThomas C. Preston and Ruth Signorell: Growth and Optical Properties of Gold Nanoshells Prior to the Formation of a Continuous Metallic Layer American Chemical Society VOL. 3 ▪ NO. 11 2009 Adam D. McFarland, Christy L. Haynes, Chad A. Mirkin, Richard P. Van Duyne, and Hilary A. Godwin: Color My Nanoworld Journal of Chemical Education Vol. 81 No. 4 April 2004 Ravi Kumar*,1, U. Bakowsky, C.M. Lehr: Preparation and characterization of cationic PLGA nanospheres as DNA carriers Biomaterials 25 1771–1777 2004 Huiyul Park, Jaemoon Yang, Sungbaek Seo, Kyujung Kim, Jinsuk Suh, Donghyun Kim, Seungjoo Haam, and Kyung-Hwa Yoo : Multifunctional Magnetic Resonance Imaging Enhancement small 2008, 4, No. 2, 192 – 196 Nanoparticles for Photothermally Controlled Drug Delivery and Thanks ! Pharmaceutical Nanotechnology Thanks ! Free gold nanoparticles easily aggregate when the environment conditions change. Here, gold nanoparticles (AuNPs) with average diameter of 3.7 nm were prepared and then modi#ed with poly(ethylene glycol) (PEG) to improve stability. The gold nanoparticles were #rst surfacemodi#ed with 3-mercaptopropionic acid (MPA) to form a self-assembled monolayer and subsequently conjugated with NH2-PEG-NH2 through amidation between the amine end groups on PEG and the carboxylic acid groups on the particles. Turkevich - Method Kumar et al. Goldpartikel PLGA-Chitosankern