First Synthesis of Multi‐Stimuli Responsive PMOEP Microgels: Phosphorus‐Based Platform for Controlled Drug Delivery

In this study, novel phosphorus‐containing and pH‐responsive poly[2‐(methacryloyloxy)ethyl phosphate] (PMOEP) microgels were successfully synthesized for the first time via emulsion polymerization using a PBzDMA‐ b ‐PMEMA diblock copolymer steric stabilizer. Their performance was systematically compared with poly[2‐(diethylamino)ethyl methacrylate] (PDEA) microgels cross‐linked with multifunctional phosphorus agents (DMEP, TMEP) and EGDMA. Dynamic light scattering (DLS) analysis demonstrated that while EGDMA‐cross‐linked PDEA microgels exhibited a volumetric swelling capacity of 3330%, PMOEP microgels reached a significantly lower swelling ratio of 594% under identical conditions. Electrokinetic and DLS measurements revealed high colloidal stability across pH 3–12. The electrophoretic mobility ( μ e ) remained consistently negative, shifting from −1.20 × 10 −8 m 2 V −1 s −1 at pH 3.3 to a maximum magnitude of −2.49 × 10 −8 m 2 V −1 s −1 at pH 11.2, providing a robust evaluation of surface charge without model‐dependent conversions for swollen soft structures. Furthermore, PMOEP microgels displayed multi‐stimuli responsiveness to pH, temperature, and salt concentration. Evaluated using Ibuprofen as a model drug under physiological conditions (pH 7.4, 37 °C), in vitro release showed a biphasic sustained profile, reaching 100% cumulative release over 113 h. These findings demonstrate that potentially biocompatible, phosphonic acid‐functionalized microgels represent a versatile platform for advanced controlled drug delivery systems.