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

Additional file 2: Table S1. of Improved Antitumor Efficacy and Pharmacokinetics of Bufalin via PEGylated Liposomes

Characterization of bufalin-loaded liposomes and bufalin-loaded PEGylated liposomes. Table S2. Inhibition of bufalin on six kinds of tumor cell lines. (DOCX 14 kb

Additional file 3: Figure S2. of Improved Antitumor Efficacy and Pharmacokinetics of Bufalin via PEGylated Liposomes

Characteristic chromatogram of bufalin in plasma. (a) Blank plasma. (b) Blank plasma spiked with bufalin. (c) Blank plasma spiked with bufalin and resibufogenin (as internal standard). (d) Plasma samples spiked with resibufogenin 30 min after intravenous administration of bufalin entity. (e) Plasma samples spiked with resibufogenin 30 min after intravenous administration of bufalin-loaded liposomes. (f) Plasma samples spiked with resibufogenin 30 min after intravenous administration of bufalin-loaded PEGylated liposomes. (1) Bufalin; (2) Resibufogenin. (TIFF 1372 kb

Additional file 1: Figure S1. of Improved Antitumor Efficacy and Pharmacokinetics of Bufalin via PEGylated Liposomes

The molecular formulas of the substances used in the formulation. (JPEG 103 kb