Localized microenvironment-modulating AgQ@GSC hydrogel microneedles for transdermal acne therapy

Acne vulgaris is driven by Propionibacterium acnes (P. acnes) colonization, oxidative stress, and inflammatory dysregulation within the pilosebaceous unit, while effective topical therapy is limited by the stratum corneum barrier and short residence time on the skin surface. Herein, we developed AgQ@GSC-MNs, an electron-beam-crosslinked hydrogel microneedle (MN) platform composed of gelatin, sodium alginate, and carboxymethyl chitosan (GSC) for co-delivery of silver nanoparticles and quercetin nanocrystals. The quercetin nanocrystals showed a mean hydrodynamic diameter of 74.1 ± 9.81 nm, and the MNs exhibited sufficient mechanical strength and successfully penetrated ex vivo mouse skin. At 72 h, the cumulative ex vivo skin permeation reached 48.9 ± 3.16% for quercetin and 5.66 ± 0.60% for total silver, while the corresponding skin retention percentages were 21.53 ± 2.95% and 15.67 ± 2.70%, respectively. AgQ@GSC-MNs exhibited antibacterial activity against S. aureus and P. acnes with extract minimum inhibitory concentrations (MICs) of 0.025 and 0.1 g/mL (patch equivalent), respectively, and exhibited antioxidant activity with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging rate of 45.26 ± 4.10%. AgQ@GSC-MNs also caused no evident macroscopic skin irritation or histopathological damage after 24 h of application. In a P. acnes-induced murine acne model, AgQ@GSC-MNs reduced the tissue bacterial burden to near-undetectable levels by day 3, suppressed tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6), and promoted lesion resolution. These findings indicate that AgQ@GSC-MNs enhance localized transdermal delivery while modulating the microbial and oxidative-inflammatory acne microenvironment.