Design of multifunctional drug delivery platforms via combinatorial synthesis

POLY 106

Douglas G. Mullen, dmullen@umich.edu, Department of Macromolecular Science and Engineering, University of Michigan, 1500 Chemistry, 930 N. University, Ann Arbor, MI 48103, Istvan J. Majoros, majoros@umich.edu, Internal Medicine, University of Michigan Center for Biologic Nanotechnology, 200 Zina Pitcher Place, Ann Arbor, MI 48109-0533, Xue-min Cheng, Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, 200 Zina Pitcher Place, Ann Arbor, MI 48109-0533, James R. Baker Jr., Nanotechnology Institute for Medicine and Biological Sciences, Univeristy of Michigan, Ann Arbor, MI 48109, Brad G. Orr, orr@umich.edu, Department of Physics, University of Michigan, Ann Arbor, MI 48109-1120, and Mark M. Banaszak Holl, mbanasza@umich.edu, Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor, MI 48109-1055.
Poly(amidoamine) (PAMAM) dendrimers have shown great promise as targeted drug delivery platforms. Studies have demonstrated that PAMAM dendrimers functionalized with targeting moieties, drug molecules, and imaging dyes efficiently induce cytotoxicity in cancer cells without causing collateral damage to healthy cells. There remain several obstacles preventing large scale utilization of multi-functionalized dendrimers including multiple time-intensive synthesis steps, decreased solubility, and an increased PDI of the final product. Thus, a new approach using a combinatorial synthesis of mono-functionalized dendrimers is being pursued. This approach utilizes the specificity of the 1,3 dipolar cycloaddition reaction between azide and alkyne moieties to create multi-functionalized dendrimer platforms that have the same clinical properties as single multi-functional dendrimers while requiring fewer synthesis steps, achieving an increased carrying capacity, and minimizing PDI. Additionally, this approach has the added capability of creating different drug-target combinations in one combinatorial step, rather than requiring the complete synthesis for each desired combination.
 

Excellence in Graduate Polymer Science Research
6:00 PM-8:00 PM, Sunday, April 6, 2008 Morial Convention Center -- Hall A, Poster

Division of Polymer Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008