Studies On The Preparation Of Freeze-dried Emodin Liposomes And Its Absorption Mechanism And Pharmacokinetics

Emodin as the major bioactive components of Polygonum cuspidatum,has bacteriostasis,anti-inflammatory,anti-cancer,liver protection and other pharmacological effects.However,for the sake of its poorly soluble,low bioavailability,long-term use can easily lead to colonic melanosis,which limits its clinical use.Liposome as a new drug carrier,while it can improve drug stability,promote drug dissolution,increase affinity for the cellsurface,and now becomes a hotspot in the research and development of herbs active components.Therefore,the emodin was made into freeze-dried emodin liposomes,and its intestinal absorption characteristics and pharmacokinetics were studied,which explores the feasibility of improving the bioavailability of emodin by liposomes as the drug delivery system.To establish the method for determine emodin by HPLC,and methodologically inspected.Using Centrifugal precipitation-microporous membrane extrusion method to isolate emodin liposomes and unencapsulated emodin,and to determine the entrapment efficiency.The determining results are accurate and rational.Based on the encapsulation efficiency as the evaluation index,three kinds of preparation methods,such as thin film dispersion method,reverse rotation steaming method and ethanol injection method,were studied.The thin film dispersion method with relatively high entrapment efficiency and low solvent residual was the preparation of emodin liposomes.Orthogonal testing design is used to select the formula which affected the entrapment efficiency of emodin liposomes.The optimal formula:the ratio of lecithin-cholesterol-emodin was 70:2:3,double-distilled water was hydrated fluid.The emodin liposomes were processed by freeze-drying,to propare freeze-dried emodin liposomes.Orthogonal testing method is used to study the prefreezing temperature,disaccharide protectant types,the ratio of sucrose-water and rehydrated fluid types,the optimal freeze-drying process: prefreezing temperature was-10?,sucrose was the protective agent,the ratio of sucrose-water was 1:10,Water for injection was rehydrated fluid.Three batches of freeze-dried emodin liposomes were prepared under the optimal process condition.The sample appearance,topographical microstructure,entrapment efficiency,particle size distribution,zeta potential,in vitro release and storage stability were investigated,in order to evaluate the quality.The sample appearance is full and loose;topographical microstructure is a uniform sphere;entrapment efficiency is 81.36%;average particle size is 206.3nm;zeta potential is-31.6mV;the sample has good sustained release properties in artificial gastric juice or artificial intestinal fluid,and can be stored for more than 3 months in a sealed atmosphere of 4 ?.The absorption characteristics of emodin and emodin liposomes in different intestinal segments of small intestine were studied by in situ single-passed perfusion model in rats.Under the conditions of mass concentration of 0.4?g/mL and perfusion rate of 0.25mL/min,the absorption rate constant(Ka)and effective permeability coefficient(Peff)were compared.The Ka of the emodin in the duodenum,jejunum,ileum and colon was increased by 50%,33%,64%,49% compared with that of emodin in each intestine.The results show that the lipsomes as the drug carrier can help improve the absorption of emodin in the small intestine.The Peff of the emodin in the duodenum,jejunum,ileum and colon was increased by 25%,42%,27% and 35%,respectively,compared with Peff of emodin in each intestine.To establish the method for determine emodin in mouse plasma and tissue homogenate by HPLC,and methodologically inspected.The emodin and emodin liposomes were orally at a dose of 0.5 mg/10 g.The plasma concentration and tissue distribution of emodin at different time points were determined.The results showed that the use of liposomes as a drug carrier helps to increase the concentration and tissue distribution of emodin at different time points.The plasma pharmacokinetics of emodin and emodin liposomes were studied by oral administration in mice,and the pharmacokinetic parameters were compared.The results showed that emodin and emodin liposomes were consistent with the first-order absorption of the two-compartment model.Emodin liposomes compared with emodin has a faster absorption rate,higher plasma concentration,longer duration of action and other advantages.It has great significance for improving the oral bioavailability of emodin.