title: Development of Safe and Potent Oil-in-Water Emulsion of Paclitaxel to Treat Peritoneal Dissemination.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. Electronic address: ogawara@pharm.okayama-u.ac.jp.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Ogawara
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fukuoka
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yoshizawa
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
authors.forename: Toshikiro
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Higaki
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism*; D065546:Drug Liberation; D004655:Emulsions / Q000008:administration & dosage* / Q000378:metabolism*; D051379:Mice; D017239:Paclitaxel / Q000008:administration & dosage* / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000378:metabolism; D011136:Polysorbates / Q000008:administration & dosage / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D016896:Treatment Outcome; D014280:Triglycerides / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; D010713:Phosphatidylcholines; D011136:Polysorbates; D014280:Triglycerides; D017239:Paclitaxel
keywords: biocompatibility; cancer; controlled release/delivery; drug delivery; emulsion/microemulsion; surfactants