Preparation of\nPaeonol Ethosomes by Microfluidic Technology\nCombined with Gaussians and Evaluation of Biological Activity by Zebrafish

Paeonol, a monoterpene glycoside compound, has extensive\npharmacological\nactivities. However, its applications are restricted by poor water\nsolubility and low bioavailability. In this study, paeonol ethosomes\n(PAE-ethosomes) were successfully prepared with a microfluidic method\nby optimizing the single factors and RSM test. The enhanced PAE-ethosomes\nwere assessed using transmission electron microscopy (TEM), Fourier\ntransform infrared spectroscopy (FT-IR), vesicle size (VS), zeta potential\n(ZP), and polydispersity index (PDI). Density functional theory analysis\nwas employed to verify the molecular interaction. The optimized RSM\nconditions were a phospholipid concentration of 6 mg/mL, a cholesterol\nconcentration of 1 mg/mL, and a total flow rate of 600 μL/min\nwith a presumed value of 60.3% and confirmation results of 61.2 ±\n0.3%. The prepared PAE-ethosomes showed better storage stability and\na slow-release effect. The <i>Q</i><sub><i>n</i></sub> of PAE-ethosomes rose from 167.0 ± 15.8 to 272.0 ±\n16.4 μg/cm<sup>2</sup> after 24 h, which was substantially greater\nthan that from a 25% hydroethanolic solution of paeonol, according\nto in vitro skin retention and transdermal absorption. The <i>Q</i><sub>s</sub> of PAE-ethosomes in the skin increased by\n225% with 265.5 ± 15.4 vs 81.8 ± 8.2 μg/cm<sup>2</sup>, compared with 25% hydroethanolic solution of paeonol. Molecular\ninteraction between paeonol and lecithin by Gaussians showed that\nthe paeonol compound may have a higher probability of spreading in\nthe hydrophilic phosphate group (“head”) position for\nthe PAE-ethosomes. The <i>Tg</i> (<i>Lyz: EGFP</i>) transgenic zebrafish results showed that PAE-ethosomes had better\nanti-inflammatory effects than paeonol. The microfluidic approach\nwas efficient with good characteristics in physics and pharmacology\nwith the potential in pharmaceutical use.