Development of Safe and Potent Oil-in-Water Emulsion of Paclitaxel to Treat Peritoneal Dissemination

作者：Ogawara Ken ichi^*; Fukuoka Yoshiko; Yoshizawa Yuta; Kimura Toshikiro; Higaki Kazutaka

来源：Journal of Pharmaceutical Sciences, 2017, 106(4): 1143-1148.

DOI：10.1016/j.xphs.2016.12.029

• drug delivery
• cancer
• biocompatibility
• emulsion/microemulsion
• surfactants
• controlled release/delivery

To develop a safer and more potent paclitaxel (PTX) formulation, we prepared various oil-in-water emulsions by using egg phosphatidylcholine, Tween 80, and a mixture of triglycerides with different fatty acid chain lengths as the cosurfactant, surfactant, and oil phase component, respectively. The mean particle diameters of the PTX-emulsions prepared were around 100 nm. The PTX-emulsions did not provoke histamine release from rat mast cells and did not show any significant hemolytic activity, suggesting that PTX-emulsions are biocompatible. In vivo antitumor activity after single intraperitoneal injection of PTX-emulsions to ascites tumor-bearing mice revealed that the formulation containing tricaproin and triacetin ( 3: 1, wt/wt, PTX-emulsion B) significantly prolonged the survival time and suppressed the accumulation of ascites fluid. Two distinct in vitro release studies showed that the release of PTX from emulsion B was significantly faster than those from other preparations. These results indicate that the adequately sustained PTX release would lead to potent in vivo antitumor activity and that PTX-emulsion B would offer an alternative approach to treat peritoneal dissemination.

• 出版日期2017-4