Protac Degraders of Androgen Receptor-Integrated Dissolving Microneedles for Androgenetic Alopecia and Recrudescence Treatment via Single Topical Administration

The research paper discusses a novel treatment for Androgenetic Alopecia (AGA), a common hair loss condition. The researchers synthesized a proteolysis targeting chimera degrader of the androgen receptor (AR-PROTAC) and integrated it with dissolving microneedles (PROTAC-MNs) to destroy AR in hair follicles. The PROTAC-MNs were found to have sufficient mechanical capabilities for precise AR-PROTAC delivery into the hair follicle-residing regions for AR degradation. A single topical application of PROTAC-MNs resulted in accelerated hair regeneration compared to daily application of minoxidil, a commonly used hair growth drug. The PROTAC-MNs also showed superior hair regeneration in AGA recrudescence, a major drawback of minoxidil. The treatment successfully regulated the signaling cascade related to hair growth and activated hair follicle stem cells without causing systemic toxicity or androgen deficiency-related chaos in vivo. The study concludes that these AR-degrading dissolving microneedles with long-lasting efficacy, one-step administration, and high biocompatibility have significant therapeutic potential for AGA treatment.