Supramolecular Polymer-Polyphenol Composite Slurries for High-fidelity Microneedle Fabrication via Ambient-temperature Pressing

Polymer microneedles (MNs) have emerged as promising next-generation transdermal drug delivery platforms owing to their noninvasive nature and high delivery efficiency. Conventional fabrication strategies for polymer MNs mainly rely on mold-assisted vacuum casting or hot pressing. However, these approaches often fail to simultaneously achieve rapid fabrication and mild processing conditions, which are particularly critical for the fabrication of temperature-sensitive drug-loaded MNs. Herein, we report a vacuum-assisted pressing strategy for MN fabrication based on O -carboxymethyl chitosan (CMCA) and natural polyphenol protocatechuic acid (PCA) supramolecular composite slurries. This method enables MN production under significantly reduced processing times (<12 h) and mild thermal conditions (50 °C). Viscoelastic supramolecular composite slurries can be obtained by precisely tuning the polymer-to-polyphenol ratio, which is highly compatible with vacuum-assisted pressing in MNs molding. The resulting polymer-polyphenol supramolecular composites exhibit robust mechanical properties, with a fracture stress of 0.5 MPa and a toughness of 1.31 MJ·m −3 . Notably, supramolecular MNs demonstrated a high fracture force of up to 1.08 N per needle, indicating sufficient mechanical integrity for transdermal insertion. This fabrication strategy offers a viable route for low-cost, scalable, and mild MN fabrication, highlighting its strong potential for practical and commercial applications.