Pharmaceutical Nanotechnology

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 Kumar et al. 1.! Synthesis 2.! Characterization 3.! Preparation of combined particles 4.! Characterization

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 Kumar et al. 1.! Synthesis 2.! Characterization 3.! Preparation of combined particles 4.! Characterization

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%) Filtration Magnetic particles Centrifugation

Turkevich - Method Kumar et al. 1.! Synthesis 2.! Characterization 3.! Preparation of combined particles 4.! Characterization

Characterization + - - + - +?

SEM TEM 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 Nanoparticles for Photothermally Controlled Drug Delivery and Magnetic Resonance Imaging Enhancement small 2008, 4, No. 2, 192 196

Thanks!

Thanks! Pharmaceutical Nanotechnology

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