Synthesis and Micellar Development of Poly[(2-isopropyl-ran-2-ethyl)-2-oxazoline]-block-poly(tert-butyl methacrylate) as Functional Bioengineered Surfactants for ARDS Treatment

Amphiphilic block copolymers based on poly(2-alkyl-2-oxazoline)s have attracted significant attention in nanomedicine due to their excellent biocompatibility and structural versatility. However, the design of well-defined micellar architectures is often limited by intrinsic challenges, including unintended homopolymer crystallization that compromises aggregate stability and poor inter-block miscibility that hinders clear microphase separation in aqueous media. To address these issues and develop an effective therapeutic platform for the acute respiratory distress syndrome (ARDS), we synthesized a functional block copolymer using poly[(2-isopropyl-ran-2-ethyl)-2-oxazoline] (PiPEtOx) as an amorphous hydrophilic segment to suppress crystallization. Hydroxyl-terminated PiPEtOx (PiPEtOx-OH) was conjugated with 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid via the Steglich coupling, and the resulting PiPEtOx macro-chain transfer agent (macro-CTA) was confirmed by ¹H NMR and GPC. The macro-CTA was sequentially polymerized to introduce an immiscible hydrophobic poly(tert-butyl methacrylate) (PtBMA) block, yielding PiPEtOx-b-PtBMA, which was further characterized by ¹H NMR and GPC. Upon dispersion in aqueous media, the self-assembly behavior of the amphiphilic block copolymers was investigated. Dynamic light scattering (DLS) was used to evaluate the formation, hydrodynamic size, and size distribution of the micelles. These results suggest that the micellar assemblies can form well-defined core–corona structures with minimal interference from the core-block crystallization.