Paclitaxel Liposome Freeze-dried Preparations

The objective of this study was to develop a good and stable taxol liposome and taxol modified liposome that have heart targeted effect. Paclitaxel is a natural product isolated from the Pacific yew tree, Taxus brevifolia. Taxol has a poor water solubility and solve in the Cremophor EL and ethanol(1:1) marketed domestic and abroad. Taxol had many disadvantages as follows:(1) The toxicity and sensitization. (2) The unstability after deliquation. To deduce the adverse effect caused by Cremophor EL, increase the solubility and stability of taxol, avoid the allergic response and keep antitumor activity deduce toxicity, taxol liposome had been studied. Because taxol exerts potent and sustained inhibitory effects on smooth muscle cell (SMC) proliferation and migration in cell culture, atenolol was added in taxol liposome to target heart.Considering its properties and the request for therapy, liposome dispersion was prepared using the film-dispersion and ethanol injection methods. Single factor test had been done and the orthogonal design was adopted to obtain the optimized prescription.Sephadex G-50 filtration chromatography was adopted to separate free drug from taxol proliposomes after hydration. Water was used to elute liposomes .The concentration of taxol in liposome was determined the EE was calculated. The result was verified by centrifugal ultrafiltration.To resolve the instability problem of liposome dispersion, freeze-drying (lyophilization) technique was utilized to prepare freeze-dried proliposome. Its main advantage is of high stability because of its solid form during preservation. It can readily and quickly reconstitute by adding water and simple stirring before use to form liposome dispersion with the same characteristics as before freeze-drying.However, freeze-drying process can induce serious and irreversible damage to liposome, including size increasing, membrane rupture, liposome infusion, membrane infolding, and the drug leakage etc. So it's of great importance to investigate the every freeze-drying process and the cryoprotectant formulation which can preserve the vesicles stable in freeze-drying. Screening from the various cryoprotectant, trehalose and mannitol were ensured to protect taxol liposome during freeze-drying.The tissue distribution of taxol and its modified liposome was initially demonstrated that taxol injection, taxol liposome and modified taxol liposome had different in vivo performance but have to be further testified.