Gradient Solvent Replacement‐Mediated Formation of High‐Strength Hydrogel‐Forming Microneedle for Long‐Term Drug Delivery
Hui Li, Fengzhen Meng, Chengwei Hu, Zhiyun Wu, Liuzhi Hao, Caijun Sun, Lijing Fang, Fan Pan, Shaoquan Bian, Huipeng Li, Mingjun Li, Bo Liu, Xiaoli Zhao
Abstract
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.