Poly(2-ethyl-2-oxazoline) as a Chemically Tunable Macromolecule inDrug Delivery: A Chemical Biology Perspective on Bioactive ExcipientSystem

Introduction: Poly(2-ethyl-2-oxazoline) (PEtOx) has emerged as a chemically tunable, biocompatible polymer with unique physicochemical properties, making it a promising nextgeneration pharmaceutical excipient. Its potential to overcome solubility and stability challenges in modern drug delivery makes it an attractive alternative to conventional polymers Methods: This review analyzed recent literature and comparative studies evaluating the physicochemical, biopharmaceutical, and regulatory aspects of PEtOx. Emphasis was placed on its role in Amorphous Solid Dispersions (ASDs), modified-release systems, nanocarriers, and hybrid formulations. Data from experimental and preclinical investigations were assessed against established excipients such as Polyvinylpyrrolidone (PVP) and Hydroxypropyl Methylcellulose (HPMC). Results: PEtOx demonstrated strong drug–polymer interactions, enabling stabilization of poorly soluble drugs at high loadings and effective inhibition of recrystallization. It improved supersaturation maintenance and dissolution performance, outperforming traditional excipients. Its non-ionic nature, low crystallinity, and tunable hydrophilicity allowed for tailored drug release in oral, transdermal, and injectable delivery systems. Additionally, PEtOx-based copolymers showed promise in mucoadhesive films, enteric coatings, and nanocarriers. Regulatory recognition, including GRAS status, further supports its translational potential. Discussion: Compared to conventional excipients, PEtOx offers advantages in stability, moisture resistance, and immunological safety. Its thermal stability and processing compatibility make it suitable for advanced manufacturing methods such as hot-melt extrusion and 3D printing. Despite these benefits, challenges remain in scalability, biodegradability, and limited clinical data. Conclusion: PEtOx represents a versatile, next-generation excipient platform with wide applicability in advanced drug delivery. Continued optimization, regulatory standardization, and clinical evaluation are critical for its successful translation into patient-centric therapeutics.