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

Abstract

SummaryCarboxylic 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 competitive aggregation model for Flash NanoPrecipitation

“…Thus, as long as there are enough unimers in the system to provide sufficient 'heterogeneous nucleation' sites for the organic, the FNP process should be nearly independent of the chemical composition of the organic (provided that it is at most weakly soluble in the non-solvent). This observation is consistent with experiments [13,[17][18][19][20][21][22][23].…”

“…A promising alternative is Flash NanoPrecipitation (FNP) [13][14][15], wherein the PSD is controlled by co-precipitating an amphiphilic di-block copolymer. The FNP process has been used to produce nanoparticles from a wide range of organic compounds [16][17][18][19][20][21][22][23]. In the FNP process, the organic compound and the block copolymer are initially dissolved in a good solvent in either a pre-mixed or in separate feed streams [13].…”

Effects of amphiphilic diblock copolymer on drug nanoparticle formation and stability

“…PCL-COCl was converted from carboxylic acid terminated PCL (PCL-COOH), which was synthesized by initiating ε-caprolactone by octanoic acid with camphor sulfonic acid as a catalyst and then was fractionated into different molecular weight in THF/methanol cosolvent. [24] $\overline{M_{\mathrm{n}}}$ was determined by NMR.…”

Efficient preparation of size tunable PEGylated gold nanoparticles

“…Further, gold nanoparticles with tunable surface chemistry can be achieved using FNP as functionalized block copolymers can be incorporated during mixing. Functionalization of the block copolymer enables conjugation to a range of small molecule or biomolecule ligands for targeted delivery or diagnostic applications15,36,37 .…”