Aluminum adjuvants are currently the most widely used adjuvants for human vaccines. However, concerns about their safety, such as local irritation at the vaccination site and potential neurotoxicity, have been raised over recent years. Herein, the bilayer microneedles are fabricated using commercially available materials and a simple micromolding preparation method in a differential dual‐release manner for sustained antigen release in the outer layer, and fast release of aluminum in the inner layer. The outer layer here replaces aluminum adjuvants to form an antigen depot, and the rapidly released adjuvants of the inner layer can activate dendritic cells, which effectively reduces the amount of aluminum while retaining their effect. The use of ovalbumin in vivo as the model antigen demonstrates that compared with subcutaneous and intramuscular injections, the bilayer microneedles achieve effective humoral immunity and relatively balanced immune response with less aluminum (1/25 of the dose), which may be related to the mechanical adjuvant effect of the microneedles. Mice treated with the bilayer microneedles show little to no aluminum accumulation in different organs, and no local irritation such as granuloma is observed. The superior vaccination safety and strong immunity using bilayer microneedles make it a promising vaccine platform.

Androgenetic alopecia (AGA) is a transracial and cross‐gender disease worldwide with a youth‐oriented tendency, but it lacks effective treatment. The binding of androgen receptor (AR) and androgen plays an essential role in the occurrence and progression of AGA. Herein, novel proteolysis targeting chimera degrader of AR (AR‐PROTAC) is synthesized and integrated with dissolving microneedles (PROTAC‐MNs) to achieve AR destruction in hair follicles for AGA treatment. The PROTAC‐MNs possess adequate mechanical capabilities for precise AR‐PROTAC delivery into the hair follicle‐residing regions for AR degradation. After applying only once topically, the PROTAC‐MNs achieve an accelerated onset of hair regeneration as compared to the daily application of the first‐line topical drug minoxidil. Intriguingly, PROTAC‐MNs via single administration still realize superior hair regeneration in AGA recrudescence, which is the major drawback of minoxidil in clinical practice. With the degradation of AR, the PROTAC‐MNs successfully regulate the signaling cascade related to hair growth and activate hair follicle stem cells. Furthermore, the PROTAC‐MNs do not cause systemic toxicity or androgen deficiency‐related chaos in vivo. Collectively, these AR‐degrading dissolving microneedles with long‐lasting efficacy, one‐step administration, and high biocompatibility provide a great therapeutic potential for AGA treatment.

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