Studies On The Gemcitabine Liposomes

Tumour is one of the main diseases affecting human's health. Due to enviromental pollution and unhealthy life style, its morbidity is increasing each year. It is approved that Gemcitabine can be beneficial for the therapy of various solid tumors, especially for the non-minicell lung cancer, pancreatic cancer and breast cancer. Both administrating alone and combinating with other anti-cancer drugs, it could produce high therapeutic effects.Gemcitabine(dFdC) is an anti-metabolism tumour drug belonging to miazines substance. Due to its half-life period, large dose (recommended 1000mg/m2) and continuing instravenous treament should be conducted in order to reach its effective conentration and the toxicity to the cancer cell. However, this toxicity can be damage to the normal tissue, suggesting that it can reduce the clinical effects.Lipsome is the bilayer vesicae consisting of phopholipid and other lipoid. It has cell-like structure which is a great potential drug carrier including biocompatibility, enhancing the therapeutic index of the drug as well as lowering toxicity. However, all of their benefits refer to the entrapment efficiency and drug-loading rate in the liposome, both of which are the main factors to evaluate the quality of the liposome. Usually, to improve the entrapment efficiency may reduce the drug-loading rate. For those low dose drugs, to reduce the drug-loadiing rate can still achieve to the clinical requirment. On the other hand, however, for those large dose drugs like Gemcitabine, both the entrapment efficiency and drug-loading rate should be considered.Here, there are some disadvantages for the gemcitabine being prepared according to the common formula and preparation method, such as high entrapment efficiency yet low drug-loading rate, both low entrapment efficiency and drug-loading rate, as well as the unstable liposome and some immature preparations. Therefore, we aim to improve the hydrochloric acid gemcitabine liposome preparations including its entrapment efficiency, drug-loading rate and stability. Based on those aspects, in the formula design, the novel membranous material cholesterol sulfuric acid ester sodium was employed to improve the affinity between drug and liposome membranous material. In the process design, DRV was used to great increase the volume of internal water phase. Then, the hydrochloric acid gemcitabine liposome with higher entrapment efficiency and drug-loarding rate was prepared.Besides, to solve the stability of the liposome, the freeze-drying technology was applied to prepare the liposome. During the preparation, the freeze-drying processing and the protective agent were investigated to optimize the processing and the formula of the protective agent. The results showed that the freeze-dried liposome remained its original characte ion temperature and time were also evaluated.Furthermore, to establish the analysis method of hydrochloric acid gemcitabine in vitro. The physicochemical properties of the blank freeze-dried liposome, such as appearance, particle diameter and pH, as well as the preliminary stability of the liposome were evaluated. The results demonstrated that after three months on the accelerated and room temperature stability studies, the freeze-dried liposome had not significant changes in terms of appearance and particle diameter, indicating its good stability.Finally, to develop a HPLC determination method of hydrochloric acid gemcitabine in rat plasma. And the pharmacodynamics of the hydrochloric acid and liposome were analyzed. The results showed that its half-life period was extended and bioavailability was significantly improved, r. The various conditions of the blank liposome loading with drug, such as incubat.