Gradient Solvent Replacement-Mediated Formation of High-Strength Hydrogel-Forming Microneedle for Long-Term Drug Delivery.

The microneedle, a minimally invasive transdermal system, provides a convenient and painless method for drug delivery. Among the various types of microneedles, hydrogel-forming microneedles (HFMs) demonstrate distinct advantages in terms of high-dose drug loading and biocompatibility. However, HFMs usually require drying to obtain sufficient puncture strength, which may destroy drug activity and increase storage costs. Herein, a high-strength HFM patch with pH-responsiveness for post-drug loading and long-term release is developed based on acrylonitrile-acrylic acid copolymer. The dipole-dipole and hydrogen bonding interactions formed through gradient solvent replacement are evenly distributed within the cross-linked network, significantly enhancing the mechanical properties of the hydrogel required for epidermal penetration. The prepared hydrogel exhibits a tensile strength of 26 MPa and a Young's modulus of 407 MPa. The microneedles formed from this hydrogel display a single needle mechanical force of 1.18 N. The post-loading mode conferred by pH responsiveness allows the drug to be encapsulated in both the tips and the substrate, acting as a reservoir. Once applied to the skin, the microneedle is activated by body fluids to achieve long-term drug release. Overall, this high-strength HFM improves the mechanical properties in the hydrated state, making it a promising minimally invasive transdermal delivery platform.