Microneedles self-implanting Astragalus polysaccharides-hybridized composite hydrogel combined with minoxidil to enhance in situ anti-androgenetic alopecia

In the current study, polysaccharides (APS) extracted from the dried roots of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao were demonstrated to promote hair regeneration. However, with an average molecular weight of 20,000, they exhibit poor transdermal absorption. To enhance local efficacy, we synthesized chemically crosslinked hyaluronic acid (cHA) and prepared γ-cyclodextrin-modified potassium metal–organic frameworks (MOFs) loaded with minoxidil (MDX) (MDX@MOF).The aforementioned materials were mixed with APS to form soluble microneedles (MDX@MOF-APS/cHA-MNs). Their oblique spike structure facilitates local fixation after skin penetration. MOF-based drug loading increased MDX water solubility by ninefold, while cHA provided significant sustained-release effects.Furthermore, APS enhances the mechanical properties of hydrogel microneedles and optimizes drug delivery. Notably, APS promotes human hair follicular papilla cell proliferation in a dose-dependent manner and exhibits synergistic effects with MDX. Concurrently, MDX@MOF-APS/cHA-MNs significantly prolong drug retention time in the skin, effectively improving hair coverage and growth rate in androgenetic alopecia mice. In summary, APS emerges as a clinical candidate for treating androgenetic alopecia, while novel microneedles with unique composition and structure enrich topical delivery strategies. Graphical abstract