# Shikonin-Loaded Nanoparticles Attenuate Particulate Matter-Induced Skin Injury by Inhibiting Oxidative Stress and Inflammation

## TL;DR

Shikonin-loaded nanoparticles reduce skin damage caused by fine particulate matter by reducing oxidative stress and inflammation.

## Contribution

A novel nanoparticle formulation of shikonin is developed to enhance its bioavailability and efficacy against PM2.5-induced skin injury.

## Key findings

- SH-NPs improved skin structure and reduced epidermal thickening and collagen fiber reduction in a mouse model.
- SH-NPs increased antioxidant enzymes and decreased markers of oxidative stress and inflammation in vivo.
- SH-NPs demonstrated high encapsulation efficiency and enhanced cellular uptake in HaCaT cells.

## Abstract

Exposure to fine particulate matter (PM2.5) poses a major threat to skin health, yet effective prevention strategies remain limited. Shikonin, a naphthoquinone derived from Lithospermum erythrorhizon, exhibits potent antioxidant and anti-inflammatory activities. However, its therapeutic application is limited by low bioavailability. To address this limitation, we developed shikonin-loaded nanoparticles (SH-NPs) using an emulsion solvent evaporation method and characterized their physicochemical properties. The protective effects of SH-NPs against PM2.5-induced skin damage were evaluated in a mouse model. The SH-NPs exhibited favorable characteristics, including a mean particle size of 209.03 ± 2.45 nm, a PDI of 0.064 ± 0.03, and a zeta potential of –17.69 ± 2.06 mV. The encapsulation efficiency is 88% and the drug loading capacity is 5.5%, respectively. In vitro, SH-NPs significantly enhanced cellular uptake in HaCaT cells. In vivo, treatment with SH-NPs significantly improved skin structural disorders, epidermal thickening, and collagen fiber reduction, while downregulating the expression of MMP-2 and MMP-9. Furthermore, SH-NPs increased the expression of SOD1 and SOD2, reduced MDA levels, and decreased the expression of TNF-α, IL-1β, and NO. In conclusion, SH-NPs attenuated PM2.5-induced skin toxicity via enhanced antioxidant, anti-inflammatory, and anti-degradation mechanisms, offering a novel strategy to boost shikonin bioavailability and prevent PM2.5-related skin damage.