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Synthesis of Heterobifunctional Thiol‐poly(lactic acid)‐ b ‐poly(ethylene glycol)‐hydroxyl for Nanoparticle Drug Delivery Applications
Author(s) -
Pagels Robert F.,
Pinkerton Nathalie M.,
York Adam W.,
Prud'homme Robert K.
Publication year - 2020
Publication title -
macromolecular chemistry and physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.57
H-Index - 112
eISSN - 1521-3935
pISSN - 1022-1352
DOI - 10.1002/macp.201900396
Subject(s) - ethylene glycol , bifunctional , peg ratio , copolymer , polymer , conjugated system , drug delivery , amphiphile , polymer chemistry , nanoparticle , chemistry , polymerization , combinatorial chemistry , materials science , organic chemistry , nanotechnology , catalysis , finance , economics
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.