Preparation of anti-cancer water-soluble paclitaxel prodrug and its anti-cancer effect / 中国药理学通报

ABSTRACT

Aim Paclitaxel(PTX)has shown an effect against human cancer. However, serious drawbacks hamper PTX clinical use.Overcoming paclitaxel limi-tations is one of the best approaches to enhance water solubility.Methods In this study,water-soluble pa-clitaxel prodrug was prepared,folic acid-polyethylene glycol-glutamic-paclitaxel (FA-PEG-Glu-PTX ) com-posed of folic acid (FA,target),amino acids (Glu, linker),and polyethylene glycol(PEG)in order to im-prove the solubilization and stability. The chemical structure and physicochemical property of prodrug were measured by LC-MS,solubility,drug release rate to e-valuate the antitumor activity and cytotoxicity of FA-PEG-Glu-PTX.MTT assays were conducted on MDA-MB-231,MCF-7,A549 and HELF cell lines.FA-PEG-Glu-PTX prodrugs were labeled with 5 amino flu-orescence visible fluorescent dye (5 AF ) for fluores-cence microscopy.Results The successful conjugation of FA-PEG-Glu-PTX was confirmed by LC-MS,and had better water solubility,release rate curve.In vitro studies indicated that foliate receptor(FR-α)mediated uptake of PTX-conjugated multi-small molecules carri-ers induced highly targeting ability,and antitumor ac-tivity,as well as reduced side toxicity effects of PTX. Conclusion FA-PEG-Glu-PTX has a good antitumor activity.