| Juglone belonging to naphthalene quinones, exists in juglandaceae plants of the genus walnuts. The juglone mainly exist in the roots, bark, leaves, green skin of walnut peel or walnut Chinese catalpa. The juglone is mainly extracted from walnut green husk at present. juglone has antibacterial, anti-inflammatory pharmacological and antitumor effects, but juglone’s poor water-solubility limit the directly use, so it’s bioavailability is low at the same time juglone’s chemical properties is not stable so it easy oxidation decomposition.Liposome as a new drug carrier, has the functions of protection core material, improve the embedding of water-soluble and improve targeting.This research intends to adopt liposome technology for preparation of juglone liposome, in order to further improve the juglone concentration in the target area and reduce the drug side effects. This study intends to build temperature sensitive liposome, in order to improve the bioavailability of juglone and provide theoretical basis for extending its applicationDialysis and dextran gel methods were applied to separate free drugs from liposomes followed by measuring encapsulated juglone using a UV spectrophotometer. 14 h was needed for dialysis method to reach dialysis equilibrium; Free drugs could be effectively separated in 30 min by dextran gel method. The content of juglone showed good linear relationship at the concentration range of 0.005 ~ 0.04 mg/mL at the wavelength of 425 nm. Through the recovery experiment, precision and reproducibility experiment confirmed that the two methods were feasible. A comparision of the two methods suggests that the dialysis method was time-consuming and the resulting value was low; the dextran gel method required less time; was more convenient and the entrapment efficiency measured was closer to the true value.Juglone liposomes were prepared by ether injection method. One-factor-at-a-time design was used to investigate the effects of five process parameters on encapsulation efficiency. Three main process parameters that influence encapsulation efficiency including lecithin/cholesterol mass ratio, lecithin/juglone mass ratio and injection speed were optimized by response surface analysis based on a three-variable, three-level Box-Behnken experimental design. The optimal conditions for preparing juglone liposomes were determined as 4.86:1 of lecithin/cholesterol mass ratio, 10.92:1 of lecithin/juglone mass ratio and 1.5 mL/min of injection speed. Under these conditions, the actual encapsulation efficiency of juglone liposomes was 79.8%, which showed a relative error of 0.033% when compared with the predictive value.In this research, thermosensitive liposomes(t-L) containing juglone were prepared with 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine(DPPC) and cholesterol by ether injection method. Morphological characteristics, encapsulation efficiency(EE), particle size, zeta potential, in vitro release, and cell viability of t-L were investigated and compared with those of conventional liposomes(c-L). Results indicated that t-L are multilamellar vesicles with lower negative charge, larger particle diameter, and higher EE than c-L. Moreover, in vitro juglone release from t-L was temperature dependent. Up to 60% of the loaded juglone was released from t-L in 20 min when environmental temperature was increased from 37 °C to 42 °C; by contrast, >60% of the drug remained inside for 24 h at 37 °C. Furthermore, MTT assay results revealed that t-L significantly increased the inhibitory effect on HepG2 cell growth and proliferation when these cells were exposed to hyperthermia. |
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