Preparation of Zoledronate liposome and its impact on apoptosis of Kupffer cells in rat liver

Abstract Purpose: To establish a method for the preparation of zoledronate liposome and to observe its effect on inducing the apoptosis of rat liver Kupffer cells. Methods: Zoledronate was encapsulated in liposomes, and then the entrapment rate was detected on a spectrophotometer. The prepared Zoledronate liposome (0.01 mg/mL) was injected into the tail vein of SD rats. Three days later, the number of Kupffer cells (CD68 positive) in rat liver tissue was detected by immunohistochemistry. Flow cytometry was used to detect the apoptosis rate of the isolated liver Kupffer cell cultured in vitro. Results: The entrapment rate of Zoledronate was 43.4±7.8%. Immunohistochemistry revealed that the number of Kupffer cells was 19.3±2.1 in PBS group and 5.5±1.7 in Zoledronate liposome group, with a significant difference (P<0.05). The apoptosis rate of Kupffer cells was 4.1±0.8% in PBS group, while it was 9±2.2% and 23.3±5.9% in Zoledronate liposomes groups with different concentrations of Zoledronate liposome (P<0.05). Conclusions: Zoledronate liposomes can effectively induce the apoptosis of Kupffer cells in vivo and in vitro, and the apoptosis rate is related to the concentration of Zoledronate liposome. To establish a rat liver Kupffer cell apoptosis model can provide a new means for further study on Kupffer cell function.

Preparation of urea-containing stable plurilamellar liposomes and studying the effect of cholesterol on their encapsulation efficiency and release rate

Liposomes have attracted much attention as a novel drug delivery system for controlled and/or targeted release of drugs. In reverse-phase evaporation, which is a well-known method of preparation for LUVs and SPLVs, the phospholipid concentration affects the preparation process, as well as characteristics of the resulting liposomes. Drug release rate from liposomes depends on permeability of the liposomal membranes. Cholesterol [CH] is quite often included in liposomal membranes to reduce their permeability to water-soluble molecules. In this study, the required concentration of the phospholipid Ovotin' 160 [O160] for the preparation of urea-containing stable plurilamellar vesicles, and the effect of different percentages of cholesterol on the encapsulation parameters and release rate of urea as a water-soluble model drug were investigated. The results show that there is a critical concentration of the phospholipid, under which the capability for the formation of a stable emulsion [in the emulsification part of the preparation process] sharply decreases. The release rate and encapsulation parameters increased when the molar ratio of cholesterol to O160 was 5% and decreased with the ratios of 50% and 100%. Therefore, in preparation of the optimum samples a balance between the encapsulation parameters as well as the release pattern should be considered carefully