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.