Preparation, pharmacokinetics and anti‐obesity effects on dogs of nuciferine liposomes

Background Nuciferine (NUC), a natural compound extracted from lotus leaves, has been proven to have anti‐obesity effects. However, the development and application of NUC as an anti‐obesity drug in dogs are hindered due to its poor water solubility and low bioavailability. Objective To promote the development of NUC‐related products for anti‐obesity in dogs, this study prepared NUC into a liposome formulation and evaluated its characteristics, pharmacokinetics in dogs, and anti‐obesity effects on high‐fat diet dogs. Methods NUC liposomes were prepared by the ethanol injection method, using NUC, egg lecithin, and β‐sitosterol as raw materials. The characteristics and release rate in vitro of liposomes were evaluated by particle size analyser and dialysis method, respectively. The pharmacokinetics in dogs after oral administration of NUC‐liposomes was carried out by the high‐performance liquid chromatography (HPLC) method. Moreover, we investigated the anti‐obesity effect of NUC‐liposomes on obese dogs fed with a high‐fat diet. Results NUC‐liposome was successfully prepared, with an EE of (79.31 ± 1.06)%, a particle size of (81.25 ± 3.14) nm, a zeta potential of (–18.75 ± 0.23) mV, and a PDI of 0.175 ± 0.031. The cumulative release rate in vitro of NUC from NUC‐liposomes was slower than that of NUC. The T1/2 and relative bioavailability of NUC‐liposomes in dogs increased, and CL reduced compared with NUC. In addition, the preventive effect of NUC‐liposomes on obesity in high‐fat diet dogs is stronger than that of NUC. Conclusions The liposome formulation of NUC was conducive to improve its relative bioavailability and anti‐obesity effect in dogs. 1. Nuciferine (NUC) has an anti‐obesity effects. However, its low bioavailability hinders the application of NUC. 2. NUC‐Liposomes made by encapsulating NUC with egg yolk lecithin and β‐sitosterol extended the half‐life of NUC, reduced clearance rate and improved the relative bioavailability of NUC in dogs. 3. NUC‐liposomes significantly reduced the body weight of high‐fat diet induced obese dogs compared with free NUC, suggesting NUC‐liposomes as potential dosage form for preventing canine obesity.