A reduced dose of Azelaic acid-loaded solid lipid nanoparticles for treatment of hyperpigmentation: In vitro characterization and cell line studies

Azelaic acid (AZA) is extensively used as a depigmenting agent due to its potential tyrosinase inhibition activity. However, due to its poor solubility and skin penetration, a higher dose (20%) is required to achieve the desired effect, which in turn is associated with unavoidable side effects. The objective of the study was to produce azelaic acid-loaded solid lipid nanoparticles (AZA-loaded SLNs) that exhibit sufficient efficacy at a lower dose (10%) while having fewer side effects. AZA-loaded SLNs were prepared with ethanol evaporation and high-pressure homogenization with a solid lipid (stearic acid) and an emulsifier (Poloxamer 188). The optimized batch (batch M4) exhibited a particle size of 281 nm, a zeta potential of-15.3 mV, an EE of 76.57%, and a sustained release pattern with 93.9% drug release in 24 h. The potent antioxidant activity of AZA-loaded SLNs was observed in the DPPH assay, which was comparable with a plain drug. In cell line studies, the 10% AZA-loaded SLNs showed potent tyrosinase enzyme inhibition and melanin content reduction than the 20% marketed cream in B16F10 melanoma cells. Primarily, 10% AZA-loaded SLNs decreased the cell cytotoxicity compared to the 20% dose that resulted in maximum cell viability. Also, it didn't show any dermal irritancy as per the obser-vations of the HET-CAM assay. Hence, 10% AZA-loaded SLNs could be an effective and safer topical treatment option for chronic hyperpigmentation at a lower dose.