Controlled Rigidity Nanolipogel-Mediated Topical Delivery of Fucosterol for Treating Androgenic Alopecia through Follicle Targeting, Promoting Angiogenesis and Inhibiting Inflammation

Androgenetic alopecia (AGA) is the most common type of hair loss. Its successful treatment depends on effective transdermal drug delivery strategies. In this study, we introduce a novel method utilizing a controlled rigidity nanolipogel (NLG) for the local delivery of fucosterol in the treatment of AGA. The NLG is formed by an identical lipid bilayer encapsulating an alginate core, with rigidity regulated by the degree of sodium alginate (SA) cross-linking. Young's moduli obtained by AFM were 2.91 ± 0.41, 61.5 ± 1.6, and 84.9 ± 1.1 MPa for the soft NLP, moderately rigid NLG-2.5, and most rigid NLG-10. In vitro skin permeation study showed that compared with the NLP and NLG-10, NLG-2.5 had the best transdermal permeability and hair follicle-targeting properties. Moreover, moderately rigid NLG-2.5 exhibited the best ability to inhibit inflammation and androgen pathways and promote angiogenesis, thereby restoring hair growth in AGA model mice. This strategy provides valuable insights for the treatment of AGA.