Biocompatible Polymeric Materials Intended for Drug Delivery and Therapeutic Applications
Chemical Product Design and Engineering (CPD&E)
Chemical Product Design & Development - IV (CPD&E - 4)
Keywords: biocompatible polymers, amphiphilic block copolymers, atom transfer radical polymerization, click chemistry
Biocompatible Polymeric Materials Intended for Drug Delivery
and Therapeutic Applications
Irakli Javakhishvili§, Desislava A. Pedersen§, Anders D. Thomsen§, Melania Bednarek¤,
Katja Jankova§, and Søren Hvilsted§
§Danish Polymer Centre, Department of Chemical Engineering,
Technical University of Denmark, Building 423, DK-2800 Kgs. Lyngby
¤Center of Molecular and Macromolecular Studies,
Polish Academy of Sciences, PL-90-365 Lodz
With the advent of the controlled free radical polymerization techniques and the novel highly efficient coupling technique (“click chemistry”1) a number of new design principles for biomedical polymeric materials emerge. We’ve recently initiated a comprehensive research programme aiming at elucidating strategies for combination of biocompatible polymers in unique but amphiphilic manners. The targeted, documented biocompatible polymers like polycapro-lactone (PCL), poly(2-methoxyethyl acrylate)2 (PMEA) with the highest known blood compatibility, poly(methyl methacrylate) (PMMA), and the two water soluble polymers, polyethylene glycol (PEG), and poly(acrylic acid) (PAA) with good mycoadhesive properties, are all prepared by living/controlled polymerization techniques.
These techniques, atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP), ensure at the same time both good molecular weight control and well defined, manageable structural end groups that sets the scene for combination of the different polymer blocks. With this tool box at hand the choice becomes to decide between all polymerization strategies or build in chemical functionalities allowing coupling of polymer blocks by “click chemistry”. An all polymerization strategy would imply preparing polymers by living/controlled techniques in such a manner that one block after polymerization can be converted to a macroinitiator enabling the second block to polymerize. The coupling strategy invariably inserts a linking unit, 1,4-triazol, resulting from the catalyzed, irreversible 1,3-dipolar cycloaddition reaction between an alkyne and an azide. Thus, this strategy necessitates the proper end functionalization of the polymeric building blocks. Fortunately the 1,4-triazol unit is FDA approved already existing in formulated drugs.
Examples of combinations of PMEA with PMMA or PEG will be elaborated. Similarly combinations of PCL with PAA (prepared from a protected precursor polymer) or PEG will be provided.
References:
1) A.D. Thomsen, E. Malmström, S. Hvilsted, J. Polym. Sci., Part A: Polym. Chem. 44 (2006) 6360-6377.
2) M. Bednarek, K. Jankova, S. Hvilsted, J. Polym. Sci., Part A: Polym. Chem. 45 (2007) in print.
Presented Thursday 20, 11:18 to 11:36, in session Chemical Product Design & Development - IV (CPD&E - 4).
