The Study On Plumonary Delivery Of Ginsenoside Rg1 Lipsomes

【Objective】To prepare ginsenoside Rg1 liposomes and evaluate the stability of Rg1-containing liposomes,and then investigate pharmacokinetics of pulmonary drug delivery in rats,which provided the theoretical and experimental basis for pulmonary delivery of ginsenoside Rg1 lipsomes.【Methods】①Rg1 liposomes were prepared with thin - film ultrasonic dispersion technology.②The three main influencing factors(mass concentration,organic solvent and phosphatidylcholine: Cholesterol) on encapsulation efficiency and the carrying amount were identified by single-factor analysis in the preparation process of Rg1 liposomes.③According to the principle of orthogonal design,the techniques of the prescription and preparation of liposomes were optimized.④The high performance liquid chromatogram(HPLC) methods wasused for the determination of encapsulation efficiency,specificity and recovery percent.⑤Transmission electron microscope was used to observe the form structure,distribution and vesicle size of Rg1 liposomes.⑥Using pH value detector and high-performance liquid chromatography instrument evaluated its stability.⑦The study of pulmonary pharmacokinetics in rats was carried out by pulmonary instillation. SPF-class healthy adult Spragne-Dawley rats(300±20g,♀:(?)=1:1) were randomly divided into 2 groups(n=12):Rg1 liposomes group and Rg1 solution group.Rg1 plasma concentrations at 0.5h,1h,1.5h,2h,2.5h,3h,24h,48h and 72h were determined by HPLC,and the pharmacokinetic parameters were calculated and analyzed by means of DAS 2.0 software.【Results】1.The optimal preparation conditions of Rg1 liposomes were selected by encapsulation efficiency and the carrying amount for the composite indicator.Only mass concentration on three factors was statistically significant(P＜0.05).Optimal concentration was 2.0 mg/mL.2.Rg1 liposomes were proved to be small unilamellar vesicle(SUV) liposomes,and the mean vesicle size of liposomes was(2.5±0.5)μm,which were quite homogeneous in size distribution.The Rg1 liposomes have a high capture efficiency of(51.20±1.5)%.3. stability of Rg1 liposomes:①The impact of different temperature on the stability:4℃/28d Rg1 liposomes was not significant changes in the appearance of uniform, declined slowly in pH,and was more stable encapsulation efficiency;25℃/ 28d Rg1 liposomes stored a little white flocculent deposition,pH value decreased rapidly,and the encapsulation efficiency more slowly declined than 4℃/28d Rg1 liposomes'.②The impact of different media on the stability:At 37℃,the encapsulation efficiency of Rg1 liposomes was 50.23%in rat plasma and the encapsulation efficiency of Rg1 liposomes placed in saline were near(P＞0.05).The concentration-time datas were all fitted to two compartment-model,and the main pharmacokinetic parameters were as follows:T1/2α=4.389 h,1.649 h,T1/2β=49.315h,42.84 h,AUC_limposome/AUC_soution= 122.67%,and AUC_limposome/AUC_iv=69.27%.Apparent absorption rate and elimination rate constants were slower than the solution's.Rg1 liposomes group's peak time was 3 h and peak concentration was 62.38 ml.Rg1 solution group's peak time was 1.5 h and peak concentration was 68.72 mL.Rg1 solution group in the administration of three days can not be detected in serum,but Rg1 liposomes group still can be detected in serum.【Conclusions】1.Ginsenoside Rg1 liposomes are proved to be small unilamellar vesicle(SUV) liposomes with spherical shape.The mean vesricle size of liposomes are 2～3μm with quite homogeneous in size distribution,which are in accordance with the request of pulmonary drug delivery.2.The mean encapsulation efficiency of Rg1 liposomes is 51.2%,which corresponded to the guidelines of Chinese Pharmacopoeia.3.Ginsenoside Rg1 liposomes stored at 4℃for one month,and no obvious changes are found in all the indices such as appearance,pH values and encapsulation efficiency,which show good stability.4.Rg1 liposomes in blood can prolong circulation and improve Rg1 bioavailability via lung approach.5. Bioavailabilty of Rg1 liposomes in rats is improved to some extent in comparison with that of Rg1 solution.