Cinnamaldehyde in a Novel Intravenous Submicrometer
Emulsion: Pharmacokinetics, Tissue Distribution, Antitumor Efficacy,
and Toxicity
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Abstract
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<sub>0–<i>t</i></sub>) 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 IC<sub>50</sub> decreasing to
0.003 and 0.001 mmol/L, respectively. The LD<sub>50</sub> 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