Synthesis of click‐reactive HPMA copolymers using RAFT polymerization for drug delivery applications |
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Authors: | Morten F. Ebbesen David H. Schaffert Michael L. Crowley David Oupický Kenneth A. Howard |
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Affiliation: | 1. Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, University of Aarhus, , 8000 Aarhus C, Denmark;2. Human Metabolome Technologies, , Cambridge, Massachusetts, 02139;3. Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, , Omaha, Nebraska, 68198‐5830 |
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Abstract: | This study describes a versatile strategy combining reversible addition fragmentation transfer (RAFT) polymerization and click chemistry to synthesize well‐defined, reactive copolymers of N‐(2‐hydroxypropyl)methacrylamide (HPMA) for drug delivery applications. A novel azide containing monomer N‐(3‐azidopropyl)methacrylamide (AzMA) was synthesized and copolymerized with HPMA using RAFT polymerization to provide p(HPMA‐co‐AzMA) copolymers with high control of molecular weight (~10–54 kDa) and polydispersity (≤1.06). The utility of the side‐chain azide functionality by Cu(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC) was demonstrated by efficient conjugation (up to 92%) of phosphocholine, a near infrared dye, and poly(ethylene glycol) (PEG) with different substitution degrees, either alone or in combination. This study introduces a novel and versatile method to synthesize well‐defined click‐reactive HPMA copolymers for preparing a panel of bioconjugates with different functionalities needed to systemically evaluate and tune the biological performance of polymer‐based drug delivery. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5091–5099 |
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Keywords: | biomaterials click chemistry drug delivery systems N‐(3‐azidopropyl)methacrylamide HPMA reversible addition fragmentation transfer (RAFT) |
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