Diatomaceous Earth-Enabled Resveratrol Microemulsion for Enhanced Permeation and Stability

This study developed a microemulsion system based on diatomaceous earth (DE) for the topical delivery of resveratrol. The microemulsions were prepared using pseudo-ternary phase diagrams. A 4:1 ethanol:virgin coconut oil ratio resulted in a larger microemulsion region than a 3:1 ratio. Two formulations with oil (ethanol:virgin coconut oil, 3:1):Cremophor RH40:water ratios of 1:5:4 (ME1) and 2:5:3 (ME2) were selected for resveratrol loading and subsequently combined with DE at ratios of DE:microemulsion (DE:ME) 0.5:1, 0.5:2, and 0.5:3. The transmission electron microscopy images demonstrated the different microstructures of the microemulsions. Rheological analysis revealed an increase in storage modulus and a decrease in the linear viscoelastic region with increasing DE concentration, particularly in ME1. Differential scanning calorimetry showed disruption of boundary water following DE incorporation. Fourier-transform infrared spectroscopy indicated primarily physical interactions between resveratrol and the DE:ME system. DE:ME demonstrated high resveratrol content, approaching 100%. DE:ME1 0.5:2 significantly enhanced resveratrol permeation, resulting in a 3-fold increase compared with the microemulsion alone after 8 h. DE:ME1 0.5:2 and DE:ME2 0.5:3 enhanced the photostability of resveratrol and the formulations remained stable after storage at 40 °C for 6 months. The DE:ME system maintained its cellular uptake capability, preserved the biological activity of resveratrol, and exhibited low cytotoxicity in human keratinocytes, with cell viability remaining above 70%. These results highlight the potential of DE-based systems for incorporating microemulsions of low-water soluble photo-sensitizing substances in topical drug delivery applications.