title: Cinnamaldehyde in a Novel Intravenous Submicrometer Emulsion: Pharmacokinetics, Tissue Distribution, Antitumor Efficacy, and Toxicity.
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(0-t)) of SME-CA showed a significantly higher value than that of CA (589 ± 59.2 vs 375 ± 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.
authors.affiliation: ‡The Cultivation Project of Collaborative Innovation Center for Chinese Medicine in QinBa Mountains, Xi'an 710032, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: ‡The Cultivation Project of Collaborative Innovation Center for Chinese Medicine in QinBa Mountains, Xi'an 710032, China.
authors.forename: Jiani
authors.initials: J
authors.lastname: Yuan
authors.affiliation: ‡The Cultivation Project of Collaborative Innovation Center for Chinese Medicine in QinBa Mountains, Xi'an 710032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: ‡The Cultivation Project of Collaborative Innovation Center for Chinese Medicine in QinBa Mountains, Xi'an 710032, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Xie
authors.affiliation: ‡The Cultivation Project of Collaborative Innovation Center for Chinese Medicine in QinBa Mountains, Xi'an 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: ‡The Cultivation Project of Collaborative Innovation Center for Chinese Medicine in QinBa Mountains, Xi'an 710032, China.
authors.forename: Siwang
authors.initials: S
authors.lastname: Wang
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D001923:Brain Chemistry; D045744:Cell Line, Tumor; D004355:Drug Stability; D004655:Emulsions; D006367:HeLa Cells; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; D000171:Acrolein; C012843:cinnamaldehyde
keywords: antitumor efficacy; cinnamaldehyde; intravenous injection; pharmacokinetics; submicrometer emulsion