Studies On The PH-sensitive Liposomes Of Vinorelbine Tartrate With Phosphatidylethanolamine

In the present study, VB was taken as the model drug to be wrapped up into pH-sensitive liposomes which were prepared by phosphatidylethanolamine by Thin-film dispersion method. VB-loaded pH-sensitive liposomes were characterized according to their physicochemical characteristics and in vitro release. In vivo pharmacokinetic characteristics and the tissue distribution in mice were investigated, which provided experiment and theoretical basis for utilizing liposomes in malignant tumor chemotherapy. The main methods and results were as follows:1. Preparation of VB pH-sensitive liposomes and physicochemical characteristics studyThe drug content of VB was determined by HPLC method. We determine the etrap efficiency of liposomes using Sephadex G-50gel colum, though which the free drugs and liposomes were separated.The VB-loaded pH-sensitive liposomes were prepared by thin-film hydration method.The entrapment efficiency was taken as the index to evaluate the effects of the temperature of rotary evaporation, stirring time, amount of CHOL and amount of OA on the characteristics of liposomes. The amount of VB, The amount of OA,and amount of CHOL were all chosen as the most influential factors, which were optimized by orthogonal design method concerning the entrapment efficiency and drug loading. The final optimized formulation was10mg of VB,60mg of PE,10mg of OA,30mg of CHOL.According to the final optimized formulation, VB-loaded pH-sensitive liposomes were prepared by adding sufficient quantum of trehalose into the homogeneous liposomes suspension, and the obtained lyophilized pH-sensitive liposomes showed good redispersibility as well as homogeneity.The optimized micelles were sphere and homogeneous in size with average particle size of298.3nm. The encapsulation efficiency, drug loading and the drug concentration of the optimized nanoparticles were (64.00±0.44)%,(7.60±0.26)%respectively.Through the study of the stability, encapsulation efficiency and drug content of freeze-dried liposome have good stability.in eight weeks, drug encapsulation efficiency and content changed scarcely.2. The in vitro drug release of VB-loaded pH-sensitive liposomesCompared with VB SOL, in vitro release results of VB-loaded pH-sensitive liposomes in in different pH value (pH were7.4,5.0,4.0,3.4), indicated that the drug release slowly from liposomes.We also found that the drug release in acidic medium was faster than that in physiological environment of pH7.4. The in vitro release of VB from micelles could be described by double phase kinetics model and regression coefficient r=0.9950. The release of VB pH sensitive liposome in the medium of pH7.4close to the dynamic mathematical models, while in the other the medium of different pH value could be described by Ritger-Peppas dynamic mathematical model.3. Pharmacokinetics and tissue distribution of VB-loaded pH-sensitive liposomes in mice after intravenousCompared with VB Sol after intravenous administration, the pharmacokinetics characteristics and tissue distribution of pH-sensitive liposomes after intravenous administration to mice were investigated. The AUCo-24h of VB-loaded micelles compared with VB suspension was224%. Because of the protectionof liposomes, the drug release was delayed in plasma, and retention time significantly, thereby exhibited a signification long-circulation property. The tissue distribution showed liposomes formulation enhanced the drug accumulation in liver, spleen and lung while lower heart and brain accumulations were discovered compared with VB Sol.These results indicated that VB-loaded pH-sensitive liposomes could offer a promising way to improve the therapeutic efficacy of anti-cancer drugs. This study provided new ideas to produce safety, reasonable, effective anticancer drugs and reaserch anti-cancer target therapy.