Nitric oxide-releasing hyaluronic acid as an antibacterial and immunomodulatory acne therapeutic.

Acne vulgaris (acne) is a common skin disorder associated with significant psychosocial impact. Current clinical therapies include topical and systemic antibiotics, benzoyl peroxide, and retinoids. While moderately effective, these clinical therapies fail to target all four major pathogenic causes of acne and are associated with painful side effects. Nitric oxide (NO), an endogenous signaling molecule, represents a promising alternative to conventional acne treatments due to its innate antibacterial and immunomodulatory functions. As NO is highly reactive, macromolecular NO donors are required for its controlled, solution-phase delivery. Prior work has utilized silica nanoparticle scaffolds to store and deliver NO, with the silica scaffold being considered inert. Herein, NO-releasing hyaluronic acid (HA), an endogenously produced biopolymer, was modified with NO donors to enable a dual-action therapeutic capable of addressing the pathogenic factors responsible for acne development. The molecular weight of these HA derivatives proved important with respect to bactericidal activity against Cutibacterium acnes and ability to modulate keratinocyte proliferation, sebum production, and inflammation.