Expanding the Scope of PROTACs: Opportunities and Challenges in Topical Delivery

The document explores the potential of PROTACs (proteolysis-targeting chimeras) for topical delivery, particularly in treating androgenetic alopecia (AGA) and other skin conditions. PROTACs offer a novel approach by degrading disease-relevant proteins, but face challenges like systemic toxicity and poor pharmacokinetics. Topical administration can mitigate these issues by localizing treatment and reducing systemic exposure. The development of microneedle technology enhances skin penetration of PROTACs, with promising preclinical results for hair regrowth. Clinical trials for PROTACs targeting androgen receptors for AGA and acne show potential for effective and safe topical treatments. The document also discusses PROTACs for atopic dermatitis and pigmentary disorders, highlighting their advantages in minimizing systemic side effects and enhancing treatment efficacy. Challenges remain in drug delivery, stability, and skin permeability, but innovative delivery systems like microneedles offer promising solutions.