Development of Safe and Potent Oil-in-Water Emulsion of Paclitaxel to Treat Peritoneal Dissemination
Development of Safe and Potent Oil-in-Water Emulsion of Paclitaxel to Treat Peritoneal Dissemination
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开发安全有效的紫杉醇水包油乳剂来治疗腹膜播散
DOI：
10.1016/j.xphs.2016.12.029
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Higaki Kazutaka
中科院分区：
文献类型：
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作者：
Ogawara Ken-ichi;Fukuoka Yoshiko;Yoshizawa Yuta;Kimura Toshikiro;Higaki Kazutaka
为了开发一种更安全和更有效的紫杉醇（PTX）的配方，我们制备了各种水包油乳剂，分别使用卵磷脂，吐温80，和不同脂肪酸链长度的甘油三酯的混合物作为助表面活性剂，表面活性剂，和油相组分。所制备的PTX乳液的平均粒径为约100 nm。PTX-乳剂没有引起组胺从大鼠肥大细胞释放，并没有显示出任何显着的溶血活性，表明PTX-乳剂是biocompatibility.In体内抗肿瘤活性后，单次腹腔注射PTX-乳剂腹水肿瘤荷瘤小鼠显示，该制剂含有三己酸甘油酯和三醋精（3：1，重量/重量，PTX-乳剂B）显着延长生存时间，抑制腹水的积累。两个不同的体外释放研究表明，从乳液B的PTX释放明显快于从其他制剂。这些结果表明，适当持续的PTX释放将导致潜在的体内抗肿瘤活性，PTX乳剂B将提供一种治疗腹膜播散的替代方法。
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 vivoantitumor 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 distinctin vitrorelease 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 potentin vivoantitumor activity and that PTX-emulsion B would offer an alternative approach to treat peritoneal dissemination.