Preparation Of Targeted Paclitaxel Liposomes And Study Of Their Drug Effect

Liposomes as drug carrier have caught more and more attention and research because of its obvious advantages. Aimed to the application of liposomes in targeted drug delivery, paclitaxel-containing liposomes were prepared and their drug effect were studied in vitro and in vivo, including the following three aspects:(1) Preparation and quality evaluation of paclitaxel-containing liposomesPaclitaxel-containing liposomes were prepared through film-sonic method and reverse phase evaporation method by using soy bean phospholipids and cholesterol. The influence of different preparation methods on size, dispersion, entrapment efficiency, as well as physical stability of paclitaxel-containing liposomes were investigated. The results showed that film-sonic method was more feasible to prepare paclitaxel-containing liposomes than reverse phase evaporation method. The as-prepared liposomes have overcome the disadvantages of paclitaxel in clinic, such as poor hydrophilicity, side effect and low bioavailability. The influence of amount of drug used in liposome preparation and dispersion buffer on size and stability of paclitaxel-containing liposomes was also studied.(2) Biomodification of liposomes and their application in cell imagingA novel liposome which could be easily surface-modified with bio-molecules containing NH2 groups was prepared by using soy bean phospholipids, cholesterol and DPPE-PEG-pNP. Anti-cytokeratins 19 antibody was connected to the surface of the liposome nanoparticles. After incubation with MGC cells and COS-7 cells, MGC cells were selectively recognized by anti-cytokeratins 19 antibody modified liposome nanoparticles and well imaged. This kind of liposomes has following advantages: surface modification can be performed efficiently and quickly under mild conditions; bio-molecules could remain high activity after modification.(3) Preparation of TMP1 peptide modified paclitaxel-containing liposome and study of targeted drug delivery in vitro and in vivoBased on the above work, applications of liposomes in targeted drug delivery were studied further. TMP1 peptide was combined to the surface of paclitaxel-containing liposomes and its targeted drug delivery was studied in vitro and in vivo. The in vitro results indicated that compared with paclitaxel-containing liposome, the viability of PE-3M-1E8 cells decreased after incubation with TMP1 modified paclitaxel-containing liposome. Also, the primary in vivo experiment results revealed that TMP1 modified paclitaxel-containing liposome and paclitaxel-containing liposome had almost the same effect of tumor inhibition, but their effects were much more superior to that of free paclitaxel.