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 m²V^-1s^-1 at pH 3.3 to a maximum magnitude of -2.49 × 10^-8 m²V^-1s^-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.