Association of Staphylococcus aureus bacteriophages and curcumin in alginate hydrogel: towards an advanced multifunctional co-delivery topical skin platform

Skin disorders are often associated with oxidative stress and bacterial infections, emphasizing the need for dual therapeutic strategies. This study explores the feasibility of co-delivering the natural bioactive compound curcumin loaded in nanostructured lipid carriers (CUR-NLCs) and Staphylococcus aureus ( S. aureus ) bacteriophages within an alginate hydrogel matrix. The objective is to develop a multifunctional system capable of delivering both antimicrobial and antioxidant agents while preserving their bioactivity. In this regard, we first studied the stability of two structurally distinct lytic S. aureus phages, ISP ( Myoviridae ) and GRCS ( Podoviridae ), in Carbopol® and alginate hydrogels. While Carbopol® formulations significantly reduced the phage lytic activity of both phages, alginate preserved it. Subsequent analyses of alginate formulations demonstrated that co-loading the hydrogel with both phages and CUR-NLCs did not significantly impair phage infectivity. Additionally, rheological characterization confirmed that the gel maintained its viscoelastic properties, indicating favorable handling properties for topical use, such as good adhesion to the skin and ease of application. Finally, release studies revealed that the alginate hydrogel enabled the simultaneous release of both bacteriophages and curcumin, while preserving their antibacterial and antioxidant properties. These findings highlight the potential of this bifunctional co-delivery system as a novel adjuvant therapy for skin conditions, offering an effective approach for managing skin conditions where both bacterial infection and oxidative stress play critical roles.