Synthesis of Heterobifunctional Thiol-poly(lactic acid)-b-poly(ethylene glycol)-hydroxyl for Nanoparticle Drug Delivery Applications

Robert F. Pagels, Nathalie M. Pinkerton, Adam W. York, Robert K. Prud'homme

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number1900396
JournalMacromolecular Chemistry and Physics
Issue number2
StatePublished - Jan 1 2020


  • block copolymers
  • conjugated polymers
  • functionalization of polymers
  • nanoparticles
  • ring-opening polymerization
  • separation techniques
  • synthesis

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Materials Chemistry
  • Polymers and Plastics
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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