Maleimide Functionalized Poly(ε‐caprolactone)‐block‐poly(ethylene glycol) (PCL‐PEG‐MAL): Synthesis, Nanoparticle Formation, and Thiol Conjugation

Carboxylic acid terminated poly(ε‐caprolactone)s (PCL‐COOHs) with narrow polydispersity were synthesized and coupled with poly(ethylene glycol) (HO–PEG–OH) to afford PCL‐PEG–OH copolymers. The hydroxyl groups in the PCL‐PEG–OHs were then converted to maleimide groups to afford maleimide terminated PCL‐PEG‐MALs that contained 70–90% maleimide functionality. Nanoparticles with maleimide functionality on their surfaces were prepared by impingement mixing. Particle sizes and size distributions were determined by dynamic light scattering. Conjugation of reduced glutathione with model maleimides and two MAL‐functional nanoparticles was also demonstrated. The amount of accessible maleimide on the particle surface was measured using Ellman's reagent to range between ≈51–67%. A versatile synthetic approach for maleimide functionalized poly(ε‐caprolactone)‐block‐poly(ethylene glycol) (PCL‐PEG‐MAL) was successfully developed. Impingement mixing of PCL‐PEG‐MAL with PCL‐PEG resulted in formation of MAL‐functionalized nanoparticles with controlled sizes and size distribution. The MAL‐functionalized particles were then modified with a model peptide through a maleimide‐thiol conjugation reaction, and the accessible maleimide was determined.