Ni–Cu Bimetallic Nanozyme and Minoxidil Co-Loaded Dissolving Microneedles Reshape Hair Follicle Microenvironment for Androgenic Alopecia Treatment
Beibei Wang, Mengcheng Tang, Yongjia Zhang, Xianan Li, Xiaoli Zhou, Han Zhang, Ruibo Zhao, Shibo Wang, Xiangdong Kong
Abstract
Androgenetic alopecia (AGA) is a prevalent dermatological disorder. Conventional minoxidil (MXD)-based therapies suffer from limitations such as low bioavailability and frequent dosing, necessitating the development of safer and more effective treatment strategies. Herein, we developed a dissolvable microneedle system (NC&MXD MNs) coloaded with nickel–copper nanozymes (NC) and MXD, which remodels the hair follicle microenvironment through synergistic dual-functional reactive oxygen species (ROS) scavenging and mechanostimulation-enhanced angiogenesis. The NC nanozymes demonstrated remarkable SOD-like and CAT-like activities, efficiently decomposing H 2 O 2 into O 2, while the microneedles achieved rapid drug release with a transdermal efficiency of 83.4% (penetration depth: 200–300 μm). Moreover, the mechanical stimulation from microneedles promoted angiogenesis and improved local blood flow. In AGA mouse models, NC&MXD MNs enhanced hair regeneration coverage to 93.7% (vs 85.1% for MXD alone), increased Ki67+ cell proliferation by 1.9-fold, and significantly thickened regenerated hair diameter. Additionally, this system reduced ROS levels by 2.3-fold and increased CD31+ vascular density by 40%, markedly improving the microenvironment. The proposed nanozyme-microneedle combinatorial strategy offers a safe, minimally invasive, and highly effective therapeutic approach for AGA.