Modular formation of hyaluronic acid/β-glucan hybrid nanogels for topical dermal delivery targeting skin dendritic cells

• Facile fabrication of hyaluronic acid/β-glucan nanogels via photopolymerization. • Topical delivery of hybrid nanogels by penetrating stratum corneum. • Enhanced nanogel uptake and maturation of dendritic cells. • Potential application for vaccination and transdermal immunomodulation. Transdermal immunomodulation is of increasing interest as an efficient drug delivery method. It non-invasively delivers drugs directly to skin-resident immune cells, thereby avoiding the first-pass metabolism. Herein, we prepared ovalbumin-conjugated hyaluronic acid-methacrylate (HAMA-OVA) and schizophyllan-methacrylate (SPGMA) hybrid nanogels and investigated their suitability for topical delivery. The particle size was controlled to between 100 and 300 nm using ultrasonication and filtering processes. The nanogels penetrated the porcine stratum corneum layer and were deposited in the dermis via hybridization with HAMA. In addition, the hybridized SPGMA promoted the internalization of the nanogels into dendritic cells (DCs; JAWSII), which resulted in an improvement in the ovalbumin delivery efficiency. In molecular biological assessments, the hybrid nanogels upregulated the DC activation marker interleukin-6 and induced DC maturation, indicating antigen-presenting behavior. These results suggest that HAMA/SPGMA hybrid nanogels are a promising topical delivery carrier for immunomodulation and vaccinations.