Authors
Mingqing Zhou, Yixuan Tang, Haowei Chen, Tianqi Liu, Yu Zhou, Jie Tan, Nanxi Xiang, Bo Ruan, Bo Yang, Jichuan Zhang, Zhenyuan Wang, Yang Shu, Fang Wang, Jiaheng Zhang
Published in
ACS applied materials & interfaces. Volume 18. Issue 33. Pages 45449-45467. Aug 26, 2026.
Abstract
A safe and effective topical therapy targeting the androgen receptor (AR), responsible for prevalent skin disorders, such as androgenetic alopecia (AGA), acne, and seborrhea, remains lacking. Macromolecular nucleic acid drugs such as siRNA have potential because of their high specificity. However, their clinical application has been hindered by the physical barrier of the stratum corneum. This study reports a hybrid nanoplatform based on cationic ionic liquid liposomes (ITD) that achieves efficient transdermal delivery of an asymmetric siRNA (asiRNA) targeting AR. This platform (particle size ∼200 nm, zeta potential +15 mV) leverages the penetration-enhancing properties of ionic liquids to improve asiRNA transdermal efficiency 8-fold and demonstrates an in vitro AR silencing efficacy comparable to that of the commercial gold-standard reagent. By silencing AR (a central androgen-responsive regulatory node shared by pilosebaceous disorders) in murine models, the formulation attenuates androgen-induced hair loss, alleviates acne-like inflammatory lesions, and reduces sebum-associated lipid accumulation. Remarkably, this preclinical pleiotropy is translated into preliminary open-label human efficacy evaluation: in a volunteer study, the formulation significantly reduced hair loss counts (-48.59%), inflammatory acne lesions (-67.74%), and skin sebum levels (-24.92%). In summary, the ITD platform represents a novel, noninvasive therapeutic strategy that addresses multiple recalcitrant androgen-dependent dermatoses, demonstrating clinical translational potential.
PMID:
42675896
Bibliographic data and abstract were imported from PubMed on 01 Sep 2026.
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