Elsevier

Polymer

Volume 50, Issue 19, 10 September 2009, Pages 4407-4423
Polymer

Feature Article
Atom transfer radical polymerization in inverse miniemulsion: A versatile route toward preparation and functionalization of microgels/nanogels for targeted drug delivery applications

https://doi.org/10.1016/j.polymer.2009.06.045Get rights and content
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open access

Abstract

This short review describes application of atom transfer radical polymerization (ATRP) in inverse miniemulsion and disulfide–thiol exchange to prepare well-defined biodegradable functional nanogels (ATRP-nanogels). Due to the formation of uniform network, the ATRP-nanogels have higher swelling ratios, better colloidal stability, and controlled degradation, as compared to nanogels prepared by conventional free-radical polymerization. Various water-soluble biomolecules such as anticancer drugs, carbohydrates, proteins, and star branched polymers were incorporated into ATRP-nanogels at high loading level, by in-situ physical loading or by in-situ chemical incorporation via covalent bonds. The nanogels crosslinked with disulfide or polyester linkages were degraded either in the presence of biocompatible reducing agents or by hydrolysis for controllable release of the encapsulated drugs. ATRP-nanogels contain bromine end groups that enable further chain extension and functionalization with biorelated molecules. They are also easily functionalized by copolymerization with functional monomers or use of functional ATRP initiator during synthesis. These functional nanogels have capability to be further chemically modified and bioconjugated with cell-targeting proteins, antibodies, and integrin-binding peptides to increase cellular uptake via clathrin-mediated endocytosis. These results suggest that such well-defined functional nanogels have great potential for targeted drug delivery applications.

Keywords

ATRP
Nanogels
Drug delivery system
Emulsion
Inverse miniemulsion

Cited by (0)

Jung Kwon Oh received his B.S. and M.S. degrees in Chemistry from Hanyang University, Korea. After over seven years of industrial research experience in emulsion polymerization, he obtained his Ph.D. degree in 2004 at the University of Toronto, Canada with Professor Mitchell A. Winnik in the field of film formation and polymer interdiffusion. He then joined the laboratory of Professor Krzysztof Matyjaszewski at Carnegie Mellon University as a recipient of a prestigious award of a Natural Science and Engineering Research Council (NSERC) Postdoctoral Fellowship of Canada. He developed there inverse miniemulsion atom transfer radical polymerization (ATRP) for synthesis, functionalization, and biomedical application of well-controlled water-soluble/crosslinked nanogels. He is currently employed at Dow Chemical Company in Midland, MI.

Sidi A. Bencherif received two First Class Honors Masters degrees in Physics and Chemistry (2000) and then in Materials and Technology Engineering (2002) from Montpellier II University in France. Sidi came to the United States in 2002 and was employed by the National Institute of Standards and Technology (NIST) as a guest researcher in the Polymer Division. In 2005, he joined the Department of Chemistry at Carnegie Mellon University. His work focused primarily on developing complex degradable synthetic and naturally derived polymeric scaffolds. In 2009, he received a Master of Science degree in Polymer Science and a Ph.D. degree in Chemistry under the supervision of Profs. Matyjaszewski and Washburn. He is currently appointed as a postdoctoral researcher in Matyjaszewski group at Carnegie Mellon. His research interests include: nanogel and star polymer synthesis via controlled radical polymerization techniques, their properties and applications; the development of novel delivery systems; biomacromolecular scaffolds; the controlled delivery of biomolecules; and the design of biomimetic materials to control stem cell fate.

Krzysztof Matyjaszewski was born in Poland in 1950. He obtained his Ph.D. degree in 1976 at the Polish Academy of Sciences in Lodz, Poland, working with Prof. S. Penczek. Since 1985 he has been at Carnegie Mellon University where he is currently J.C. Warner University Professor of Natural Sciences and director of Center for Macromolecular Engineering. His main research interests include controlled/living radical polymerization, catalysis, environmental chemistry, and the synthesis of advanced materials for optoelectronic and biomedical applications. He has co-authored over 600 publications, including 13 monographs and books as well as over 40 US and 100 international patents. His citation record exceeds 30,000 for the last decade and ranks him 3rd in all fields of chemistry. He has formed two industrial consortia focused on controlled radical polymerization at Carnegie Mellon with over 40 international members. He has received doctorate honoris causa from 5 universities, the 2009 Presidential Award in Green Chemistry and several awards from the American Chemical Society, and other institutions. He is a member of US National Academy of Engineering and Polish Academy of Sciences.