【摘 要】
：
Paclitaxel (Taxol(R)),a microtubule inhibitor,has been widely used as a chemotherapeutic agent.However,the injectable taxol formulation to overcome poor solubility has created serious side effects tha
【机 构】
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Louisiana State University Agricultural Center USA
【出 处】
：
中国上海第七届国际新药发明科技年会
论文部分内容阅读
Paclitaxel (Taxol(R)),a microtubule inhibitor,has been widely used as a chemotherapeutic agent.However,the injectable taxol formulation to overcome poor solubility has created serious side effects that often limit its therapeutic dose range.An improved formulation by binding paclitaxel to albumin (a nanoparticle protein based platform) to deliver the drug has been marketed under the drug name Abraxane.We attempted to solubilize paclitaxel by using a new class of proprietary complexing agents (different from cyclodextrins).It was found that in the presence of 20% w/v complexing agents,a water solution containing 210μ g/mL of paclitaxel was obtained.This solubilized paclitaxel water solution is stable for at least four weeks,when diluted with PBS solution by 20-fold,and in pH range of 1.5 to 7.4.In vitro cytotoxicity assays against three human cancer cell lines found paclitaxel delivered as water-soluble drug-solubilizer complexes had IC50 of 4.9nM,13.7nM,or 74.8nM against PANC-1 (human pancreatic),PC3 (human prostate),or A549 (human lung) cancer cells.The new natural complexing agents appear to be superior to cyclodextrins and may provide a new tool for developing new and better paclitaxel formulations for parenteral,topical,ocular,oral,and transdermal applications.
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