| The paper includes the following sections:Part 1 Literature ReviewThe paper first of all has summarized the research progress of liposome delivery systems, biophysical techniques for the progress of the biological membrane phase state, Caco-2 cell lines in vitro model and its pharmaceutical applications of research progress, as well as the pharmacological effects of ginsenoside Rgl and its pharmacokineticsthe studies were reviewed.Part 21 Establishment of the determination method for ginsenoside Rgl Determined ginsenoside Rgl by HPLC. The linear range of ginsenoside Rgl was 7.415ng-2996.172ng respectively, and the repeatability,the recovery and stability of the methods met the requirements. MarvinSketch software was selected to predict the physicochemical parameters of ginsenoside Rgl.The molecular weight of ginsenoside Rgl was calculated to be 800.492207012, logP value was 0.68,10 H bond donor and 14 H bond acceptor was contained. All these parameters predicted that ginsenoside Rgl had poor oral absorption.2 Optimization preparation of ginsenoside Rgl liposome by central composite design and response surface methodTo study the preparation method of ginsenoside Rgl (Rgl) liposome and to screen the optimal technological conditions by the encapsulation efficiencies for ginsenoside Rgl,liposomes were made of dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol (CH) or stigmasterol (ST) by film evaporation technique, then response surface methodology was adopted to screen the optimal conditions. The optimal technological conditions of Rgl/DPPC/CH liposome were as follows:the quality percentage content of Rgl was 7.4～8.1%, the hydration time was 50.0～85.0min,the hydration temperature was 60.0～63.0℃.The optimal technological conditions of Rgl/DPPC/ST liposome were as follows:The quality percentage content of Rgl was 7.6～8.1%, the hydration time was 95.0～100.Omin,and the hydration temperature was 40.0～63.0℃. The central composite design and response surface methodology is suitable for optimizing the formulation. Stigmasterol could be used in the formulation of ginsenoside Rgl liposome.3 Study of interaction between Ginsenoside Rg1 and liposomes employing DSC,XRD and Ramam techniquesTo investigate molecular interaction among ginsenoside Rgl, cholesterol/ stigmasterol and phospholipid in ginsenoside Rgl-encapsulated liposomes, liposomes were made of dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol or stigmasterol,and ginsenoside Rgl,then differential scanning calorimetry (DSC),synchrotron x-ray diffraction (XRD) techniques and raman spectra (Raman) were employed to investigate molecular interaction among ginsenoside Rgl, cholesterol/stigmasterol and DPPC in ginsenoside Rgl-encapsulated liposomes. DSC curve displayed two endothermal peaks and curves of SAXS displayed two signals of phase transition when the concentration of ginsenoside Rgl was increased to 20% in ginsenoside Rgl/cholesterol/DPPC liposomes, but in ginsenoside Rgl/stigmasterol/DPPC liposomes,curves of DSC and SAXS just show one signal, Raman spectroscopy results showed that the liposome membrane fluidity changed with the addition of ginsenoside Rg1.Stigmasterol could be used in the formulation of ginsenoside Rgl liposome.4 Transport characteristics of ginsenoside Rgl and its liposome in Caco-2 cell monolayersTaken out the freezing of Caco-2 cells, put them into water(37℃), quickly thawed, then moved to the 10% FBS MEM medium at 37℃,90% of relative humidity and the 5% CO2 concentration. Replaced the medium every other day, when the cells reached approximately 80% confluence (Caco-2 cells basically covered sidewall), digested them with 0.25% trypsin-EDTA.2.0×105/cm2 density of Caco-2 cells were vaccinated to 12-well Millicell board. Transmembrane resistance values and Lucifer Yellow CH transmembrane transport experiments used Caco-2 cell monolayer model to evaluate; MTT method was used to evaluate the drug on the inhibition of Caco-2 cells, selected the solvent inhibition rates<5%, the test substance the inhibition rate of<10%, as the appropriate dose experiments; studied the influencing factors on Caco-2 cell uptake experiments, including the effects of incubation time on uptake in Caco-2 and pH on the intake of drugs in Caco-2, the temperature Caco-2 uptake of drugs and drug concentration on the uptake by Caco-2 cells the impact, and the drug transmembrane transport experiments.The results showed that liposomes can destroy the ordered arrangement of the cell membrane lipid bilayer, thus helping to promote drug absorption, cholesterol liposome and beans steroid liposome for ginsenoside Rgl intestinal absorption was similar.5 Bioavailability Assessment of ginsenoside Rgl liposomesTo assess the Bioavailability of ginsenoside Rgl liposomes, plasma concentrations were determined by HPLC, Kinetica was used to process main pharmacokinetics parameters. The results showed that two kinds of ginsenoside Rgl liposomes'Tmax increased. The AUC results indicated that the ginsenoside Rgl/DPPC/ST liposomes can significantly improve the bioavailability in rats, preparations of ginsenoside Rgl liposomes meets the desired objectives.
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