Cinnamaldehyde in a Novel Intravenous Submicrometer Emulsion: Pharmacokinetics, Tissue Distribution, Antitumor Efficacy, and Toxicity

The purpose of our research is to find a new lipid emulsion to deliver a low water-soluble compound, cinnamaldehyde (CA). Its characteristics, pharmacokinetics, antitumor efficacy, and toxicity were evaluated. The mean particle size, zeta potential, and encapsulation efficiency of the submicromemter emulsion of CA (SME-CA) were 130 ± 5.92 nm, −25.7 ± 6.00 mV, and 99.5 ± 0.25%, respectively. The area under the curve from 0 h to termination time (AUC_0–<i>t</i>) of SME-CA showed a significantly higher value than that of CA (589 ± 59.2 vs 375 ± 83.5 ng h/L, <i>P</i> < 0.01). Tissue distribution study showed various changes; among them, a 27% higher concentration was found in brain tissue when using SME-CA at 15 min after administration. For the efficacy evaluation, SME-CA exhibited 8- and 11-fold antitumor activity in the depression of HeLa and A549 cell lines with the IC₅₀ decreasing to 0.003 and 0.001 mmol/L, respectively. The LD₅₀ values of CA and SME-CA in mice were 74.8 and 125 mg/kg, suggesting increased safety from the new formulation. The new formulation exhibited lower toxicity, higher antitumor activity, and a more satisfactory pharmacokinetic property, which displayed great potential for future pharmacological application