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

TY - JOUR

T1 - Synthesis of click-reactive HPMA copolymers using RAFT polymerization for drug delivery applications

AU - Ebbesen, Morten F

AU - Schaffert, D.H.

AU - Crowley, Michael L

AU - Oupický, David

AU - Howard, Ken

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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

AB - 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

UR - http://www.scopus.com/inward/record.url?scp=84886600901&partnerID=8YFLogxK

U2 - 10.1002/pola.26941

DO - 10.1002/pola.26941

M3 - Journal article

AN - SCOPUS:84886600901

SN - 0887-624X

VL - 51

SP - 5091

EP - 5099

JO - Journal of Polymer Science. Part A, Polymer Chemistry

JF - Journal of Polymer Science. Part A, Polymer Chemistry

IS - 23

ER -