Preparation of Polyester Microspheres by Passerini Three-Component Dispersion Polymerization in Water

Aqueous dispersion polymerization, predominantly based on the mechanism of radical polymerization, presents inherent limitations for polyester preparation through polycondensation or ring-opening polymerization approaches due to the substantial presence of water molecules. Herein, we report a facile and versatile strategy for the preparation of polyester microspheres (PEMs) via Passerini three-component dispersion polymerization (P-3CDP) under ambient aqueous conditions. By optimizing the polymerization parameters, we successfully synthesized a library of PEMs featuring diverse main-chain structures, including aliphatic carbon chains and functional backbones incorporating phenyl, alkenyl, biobased isosorbide, and furfuryl moieties, as well as reduction-responsive disulfide and pH-responsive Boc-protected l-glutamic acid groups. Comprehensive characterization of the resulting PEMs, including their chemical structures, microsphere morphologies, molar masses, and thermal properties, was performed using 1H NMR, SEM, DLS, SEC, and DSC measurements. CCK-8 assays with mBMSC cells were conducted to assess the cytotoxicity and verify biological safety. Taking the PEM containing a Boc-protected l-glutamic acid backbone as an example, its pH-responsive self-immolative property was verified, suggesting the feasibility of straightforward preparation of stimuli-responsive PEMs through the aqueous P-3CDP method.