Caffeic acid–functionalized silver nanoparticles for skin therapy: Antioxidant, antibacterial, and anti-melanogenic properties

Identifier:  imarina:9470719

Handle: https://hdl.handle.net/20.500.11797/imarina9470719

Authors:  Bouaouz S; Lozano R; Bravo FI; Muguerza B; Mulero M; Calvo E; Ortega P; de la Mata FJ

Abstract:
Multifunctional nanomaterials offers promising strategies for the treatment of skin disorders involving oxidative stress, microbial infections, and hyperpigmentation. Herein, we report the covalent functionalization of silver nanoparticles AgNP-(S-PEG2K-CA) (AgNP-1) with caffeic acid, a natural polyphenol with well-known antioxidant and anti-melanogenic properties. Additionally, a cationic carbosilane wedge was introduced to confer antibacterial functionality, resulting in a heterofunctional nanoconjugate, AgNP-(S-PEG2K-CA)(S-G<inf>1</inf>-NMe<inf>3</inf>Cl) (AgNP-2) , with enhanced biological performance. The physicochemical characterization confirmed successful functionalization and stability of the nanoparticles. Biological assays showed that the silver nanoparticles exhibited antioxidant activity (AgNP-1: IC<inf>50</inf> = 4.18 μg/mL, EC<inf>50</inf> = 0.57 μg/mL; AgNP-2: IC<inf>50</inf> = 12.35 μg/mL, EC<inf>50</inf> = 0.87 μg/mL), which was attributed to the presence of caffeic acid on their surface and AgNP-2 exhibited strong antibacterial effects, particularly against Staphylococcus aureus (MIC 4 mgL⁻¹ and MBC 8 mgL⁻¹) and Escherichia coli (MIC 4 mgL⁻¹ and MBC 8 mgL⁻¹). In vitro experiments using a mammalian melanocyte model (B16F10 cells) revealed for both nanoparticles significantly inhibited melanin synthesis at 20 μg/mL reduced the accumulation of intracellular melanin in a similar extent as kojic acid at 1000 μg/mL. Finally, permeation studies using Franz diffusion cells, combined with UV–Vis spectroscopy and ICP-OES analysis to detect nanoparticle concentration, showed that neither AgNP-1 nor AgNP-2 were able to cross the membrane, indicating that they remain confined to the membrane surface. This localization is crucial for minimizing the risk of systemic exposure, thereby supporting the safety and suitability of these nanoparticles for topical applications.