TY - JOUR
T1 - Synthesis of Heterobifunctional Thiol-poly(lactic acid)-b-poly(ethylene glycol)-hydroxyl for Nanoparticle Drug Delivery Applications
AU - Pagels, Robert F.
AU - Pinkerton, Nathalie M.
AU - York, Adam W.
AU - Prud'homme, Robert K.
N1 - Funding Information:
The authors would like to thank Evonik Industries (Essen, Germany) for generously supplying the PLA homopolymer used as the nanoparticle core in this work. This work was supported by Optimeos Life Sciences (Princeton, NJ) and the Helene Shipley Hunt Fund. R.F. Pagels was supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGA 1148900.
Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Biocompatible, amphiphilic block copolymers, such as poly(lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG), that can be conjugated to targeting ligands, therapeutics, and imaging agents are required for the development of polymeric nanoparticle drug delivery systems. Synthesis of targetable, heterobifunctional X-PLA-b-PEG-Y has required the use of heterobifunctional PEG, which involves specialty equipment to synthesize and is expensive to purchase. Herein, a new method for the synthesis of bifunctional HS-PLA-b-PEG-OH is described. The approach takes advantage of polymer solution properties to improve a critical purification step, and uses inexpensive and readily available PEG-diol as a starting material. In the method demonstrated here, the ring-opening polymerization of PLA is initiated by both ends of a cleavable bifunctional initiator. PEG is conjugated to each PLA end, resulting in a high molecular weight intermediate which is simple to purify from the excess PEG, with recoveries that are nearly three times higher than when a monofunctional initiator is used. Following purification, the triblock copolymer is cleaved to produce the final HS-PLA-b-PEG-OH product, in which both polymer ends are reactive. Moreover, the polymers successfully stabilize nanoparticles produced by Flash NanoPrecipitation. Importantly, the synthesis method can be adopted by non-polymer experts.
AB - Biocompatible, amphiphilic block copolymers, such as poly(lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG), that can be conjugated to targeting ligands, therapeutics, and imaging agents are required for the development of polymeric nanoparticle drug delivery systems. Synthesis of targetable, heterobifunctional X-PLA-b-PEG-Y has required the use of heterobifunctional PEG, which involves specialty equipment to synthesize and is expensive to purchase. Herein, a new method for the synthesis of bifunctional HS-PLA-b-PEG-OH is described. The approach takes advantage of polymer solution properties to improve a critical purification step, and uses inexpensive and readily available PEG-diol as a starting material. In the method demonstrated here, the ring-opening polymerization of PLA is initiated by both ends of a cleavable bifunctional initiator. PEG is conjugated to each PLA end, resulting in a high molecular weight intermediate which is simple to purify from the excess PEG, with recoveries that are nearly three times higher than when a monofunctional initiator is used. Following purification, the triblock copolymer is cleaved to produce the final HS-PLA-b-PEG-OH product, in which both polymer ends are reactive. Moreover, the polymers successfully stabilize nanoparticles produced by Flash NanoPrecipitation. Importantly, the synthesis method can be adopted by non-polymer experts.
KW - block copolymers
KW - conjugated polymers
KW - functionalization of polymers
KW - nanoparticles
KW - ring-opening polymerization
KW - separation techniques
KW - synthesis
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U2 - 10.1002/macp.201900396
DO - 10.1002/macp.201900396
M3 - Article
AN - SCOPUS:85076608240
SN - 1022-1352
VL - 221
JO - Macromolecular Chemistry and Physics
JF - Macromolecular Chemistry and Physics
IS - 2
M1 - 1900396
ER -