N-Hydroxyethyl acrylamide

• CAS: 7646​-67-5
• Catalog Number: ACM7646675-1
• Category: Main Products
• Molecular Weight: 115.13
• Molecular Formula: C₅H₉NO₂
• Appearance: colourless liquid

Case Study

N-Hydroxyethyl Acrylamide as a Hydrophilic Comonomer for pH-Responsive Drug Delivery Hydrogels

Bal, Ayça, et al. Journal of applied polymer science 133.13 (2016).

N-Hydroxyethyl acrylamide (HEAA) is a hydrophilic, non-ionic monomer that, when copolymerized with methacrylic acid (MAA) and acrylamide (AAm), forms pH-responsive terpolymer hydrogels. The HEAA units provide additional hydrogen-bonding sites and enhance biocompatibility without compromising the pH sensitivity imparted by MAA.
Fabrication Process: Terpolymers of MAA, AAm, and HEAA (with fixed AAm:HEAA ratios) were synthesized by free-radical polymerization in aqueous solution using N,N'-methylenebisacrylamide as crosslinker and APS/TEMED as initiator. Hydrogels were cast in glass tubes at 60 °C for 24 h, then washed and vacuum-dried.
Performance Evaluation: FTIR confirmed the presence of HEAA (broad O-H/N-H stretch at 3440 cm^-1, amide I/II bands). The terpolymers exhibited pH-dependent swelling: at pH 7.4, the gel with highest MAA content (T2-MAH) swelled to 21.9 g H2O/g polymer, versus 17.6 g/g at pH 2.1. The MAA-free copolymer (CO-AH, AAm+HEAA) showed no pH response (~13.5 g/g at both pH). Drug loading capacity for nadolol increased with MAA content (200.2 mg/g for T2-MAH). In vitro release at pH 7.4 followed Higuchi kinetics (R² = 0.991), indicating diffusion-controlled release.
Conclusion: HEAA serves as a hydrophilic, non-responsive building block that, together with MAA, enables pH-triggered swelling and sustained drug release, suitable for intestinal delivery.

N-Hydroxyethyl Acrylamide as an Antifouling Brush Monomer for Protein-Resistant Nanoparticles

Qin, Xue, et al. Colloids and Surfaces B: Biointerfaces 155 (2017): 408-414.

N-Hydroxyethyl acrylamide (HEAA) is a hydrophilic, non-ionic monomer that, when polymerized as a surface-grafted brush on polystyrene (PS) nanoparticles via surface-initiated photo-emulsion polymerization, imparts exceptional stability and resistance to nonspecific protein adsorption in biological media.
Fabrication Process: PS core nanoparticles (~100 nm) were first coated with a photoinitiator layer (PS@HMM). HEAA (150 wt% relative to core) was then polymerized under UV irradiation for 2.5 h to form PS@PHEAA with a brush thickness of ~46 nm.
Performance Evaluation: FTIR confirmed PHEAA grafting (amide I at 1662 cm^-1, amide II at 1558 cm^-1, broad O-H/N-H at 3450 cm^-1). PS@PHEAA diameters remained constant at 210 ± 5 nm over pH 3-11 and at various ionic strengths for 120 h. In single-protein solutions (BSA or lysozyme), particle size and polydispersity did not change. Isothermal titration calorimetry showed weak, non-specific binding (ΔG ~ -7.8 kcal/mol) with enthalpy-driven interaction for BSA and entropy-driven for lysozyme. In 10% fetal bovine serum, PS@PHEAA maintained size change below 15 nm over 43 h, whereas bare PS cores aggregated severely.
Conclusion: HEAA-based polymer brushes provide robust antifouling protection, making them ideal for biomedical nanoparticle applications.

N-Hydroxyethyl Acrylamide as a Functional Initiator for Enzymatic Ring-Opening Polymerization and Nanoparticle Formation

Lentz, Joachim C., et al. Polymer chemistry 13.42 (2022): 6032-6045.

N-Hydroxyethyl acrylamide (HEAA) is a stable, functional initiator for the enzymatic ring-opening polymerization (eROP) of ε-caprolactone and δ-valerolactone using Novozym 435 (CALB). Unlike 2-hydroxyethyl methacrylate (HEMA), HEAA does not undergo transesterification, enabling clean synthesis of acrylamide-terminated polyesters for subsequent radical copolymerization and nanoparticle assembly.
Fabrication Process: HEAA, lactone (CL or VL), and 2-MeTHF (bio-based solvent) were reacted at 65 °C with 10 wt% Novozym 435 for 5 h. The resulting HEAA-PCL macromonomer was then copolymerized with PEGMA via free-radical polymerization (AIBN, 65 °C). Nanoparticles were formed by nanoprecipitation in water.
Performance Evaluation: ¹H NMR showed stable HEAA (no self-reaction) but incomplete initiator consumption (e.g., 41% conversion for CL at 1:20 ratio). Computational docking revealed that HEAA-CL binds more strongly to CALB than HEAA, causing faster propagation than initiation. Chain extension with lactide confirmed hydroxyl end-group fidelity via organocatalysis. HEAA-PCL-co-PEGMA copolymers self-assembled into nanoparticles (hydrodynamic diameter ~105-140 nm, PDI < 0.25). Cytotoxicity assays (Caco-2, A549, A431 cells) showed >80% viability and low LDH release at 500 μg/mL.
Conclusion: HEAA is a robust, metal-free eROP initiator that enables degradable, amphiphilic polymers for safe nanoparticle drug delivery.