A Surfactant‐Mediated Strategy to Modulate the Self‐Assembly and Drug Delivery Efficacy of Block Copolymers

ABSTRACT Although amphiphilic PEO‐PPO block copolymers are promising drug carriers, their aggregation stability and release controllability require further optimization. In this study, a novel hyperbranched copolymer, A4, featuring 18 branching points and three aromatic rings in its core, was designed and synthesized. Compared with the conventional star‐shaped copolymer T1304, A4 exhibited a lower cloud point and larger aggregate size, demonstrating superior drug carrier properties. Beyond molecular design, a surfactant‐mediated strategy was introduced to precisely modulate the self‐assembly behavior and drug delivery performance. By incorporating cationic dodecyl trimethyl ammonium bromide (DTAB), anionic sodium dodecyl sulfate (SDS), and nonionic Tween 20, it was demonstrated that the molecular interactions between surfactants and copolymers critically govern the thermodynamic and structural properties of aggregates. Specifically, ionic surfactants embedded their hydrophobic tails into the PPO core, reducing the critical aggregation concentration and promoting the formation of larger, more stable vesicles with high drug loading capacity and sustained release profiles. In contrast, Tween 20 enhanced the hydration shell, resulting in smaller aggregates and accelerated drug release. This work elucidates the pivotal role of surfactant type in regulating the self‐assembly and drug delivery performance of PEO‐PPO copolymers, providing valuable insights for developing efficient, tunable nanocarriers to advance block copolymer applications in pharmaceutical delivery.