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

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• 作者：Hang Zhao ; Jiani Yuan ; Qian Yang ; Yanhua Xie ; Wei Cao ; Siwang Wang
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2015
• 出版时间：July 22, 2015
• 年：2015
• 卷：63
• 期：28
• 页码：6386-6392
• 全文大小：349K
• ISSN：1520-5118

文摘

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 卤 5.92 nm, 鈭?5.7 卤 6.00 mV, and 99.5 卤 0.25%, respectively. The area under the curve from 0 h to termination time (AUC_0鈥?i>t) of SME-CA showed a significantly higher value than that of CA (589 卤 59.2 vs 375 卤 83.5 ng h/L, P < 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.