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To illustrate the effects of premixing propofol lipid emulsion (PLE) and fentanyl citrate (FC) on acute toxicity, sedation, and analgesia, sixty female mice were randomly assigned to individual and premixed groups. The median lethal dose (LD50), median effective dose (ED50) of loss of righting reflex, and ED50 of tail flick test in both groups were determined using the up and down procedure (FC : PLE = 1 μg : 2 mg). PLE was immediately administered to the mice from the individual group via the tail vein after injecting FC. By contrast, FC was mixed with PLE before injection from the premixed group. No significant differences in LD50, histopathological examination, and ED50 sedation value were found between the groups. However, ED50 of analgesia in the premixed group decreased to half of that in the individual group. Transmission electron microscopic observation revealed ~10 nm fusiform particles at the juncture of 200–300 nm particles in the mixture of PLE and FC compared with the single PLE and its mixture with saline, which may be attributed to the structure of FC. In conclusion, premixing PLE and FC enhanced synergic analgesia twofold but did not influence toxicity and sedation compared with individual injections

Nanoformulation of Premixing Propofol Lipid Emulsion and Fentanyl Citrate and Their Effects on Acute Toxicity, Sedation, and Analgesia