Synthesis of click-reactive HPMA copolymers using RAFT polymerization for drug delivery applications

Morten F. Ebbesen, David H. Schaffert, Michael L. Crowley, David Oupicky, Kenneth A. Howard

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5091-5099
Number of pages9
JournalJournal of Polymer Science, Part A: Polymer Chemistry
Volume51
Issue number23
DOIs
StatePublished - Dec 1 2013

Fingerprint

Drug delivery
Azides
Copolymers
Polymerization
Polyethylene glycols
Cycloaddition
Polydispersity
Phosphorylcholine
Alkynes
Substitution reactions
Dyes
Monomers
Molecular weight
Infrared radiation
Polymers
Coloring Agents
N-(2-hydroxypropyl)methacrylamide
methacrylamide

Keywords

  • HPMA
  • N-(3-azidopropyl) methacrylamide
  • biomaterials
  • click chemistry
  • drug delivery systems
  • reversible addition fragmentation transfer (RAFT)

ASJC Scopus subject areas

  • Materials Chemistry
  • Polymers and Plastics
  • Organic Chemistry

Cite this

Synthesis of click-reactive HPMA copolymers using RAFT polymerization for drug delivery applications. / Ebbesen, Morten F.; Schaffert, David H.; Crowley, Michael L.; Oupicky, David; Howard, Kenneth A.

In: Journal of Polymer Science, Part A: Polymer Chemistry, Vol. 51, No. 23, 01.12.2013, p. 5091-5099.

Research output: Contribution to journalArticle

Ebbesen, Morten F. ; Schaffert, David H. ; Crowley, Michael L. ; Oupicky, David ; Howard, Kenneth A. / Synthesis of click-reactive HPMA copolymers using RAFT polymerization for drug delivery applications. In: Journal of Polymer Science, Part A: Polymer Chemistry. 2013 ; Vol. 51, No. 23. pp. 5091-5099.
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