Development of Curcumin and Turmerone Loaded Solid Lipid Nanoparticle for Topical Delivery: Optimization, Characterization and Skin Irritation Evaluation with 3D Tissue Model

Background: Curcuma longa L., commonly known as turmeric, is renowned for its therapeutic benefits attributed to bioactive compounds, namely curcumin (Cur) and aromatic turmerone (Tur), present in its rhizome. These compounds exhibit diverse therapeutic properties, including anti-inflammatory, antioxidant, and anti-tumor effects. However, the topical application of these compounds has a significant potential for inducing skin irritation. This study focuses on formulating solid lipid nanoparticle (SLN) carriers encapsulating both Cur and Tur for reduced irritation and enhanced stability. Methods: SLN formulations were prepared by a method using homogenization followed by ultrasonication procedures and optimized by applying response surface methodology (RSM). Results: The optimized SLN formulation demonstrated entrapment efficiencies, with 77.21 +/- 4.28% for Cur and 75.12 +/- 2.51% for Tur. A size distribution of 292.11 +/- 9.43 nm was obtained, which was confirmed to be a spherical and uniform shape via environmental scanning electron microscopy (ESEM) images. The in vitro release study indicated cumulative releases of 71.32 +/- 3.73% for Cur and 67.23 +/- 1.64% for Tur after 24 hours under sink conditions. Physical stability tests confirmed the stability of formulation, allowing storage at 4 degrees C for a minimum of 60 days. Notably, in vitro skin irritation studies, utilizing the reconstructed human epidermal model (EPI200-SIT), revealed a significant reduction in irritation with the SLN containing Cur and Tur compared to nonencapsulated Cur and Tur. Conclusion: These findings collectively endorse the optimized SLN formulation as a favorable delivery system for Cur and Tur in diverse topical uses, offering enhanced stability, controlled release and reduced irritation.