Self-emulsifying O/W formulations of paclitaxel prepared from mixed nonionic surfactants.
Nonionic self-emulsifying oil-in-water (O/W) formulations free of Cremophore were developed as drug delivery vehicles for paclitaxel. The surfactants used included phosphatidylcholine purified from egg yolk (EPC), Tween, and Span. Oils phases were either pure components or blends from benzyl alcohol, 2-phenylethanol benzyl benzoate, and tributyrin. Among these surfactants, mixtures of EPC and Tween-80 gave really stable emulsions in proper sizes ranging from 70 to 200 nm, mainly depends on the ratio of EPC to Tween-80 and amount of oils. Paclitaxel could be well preserved without any loss in oily stocks, namely mixtures of oils and paclitaxel as well as surfactants, stored at 4 degrees C for more than 8 months. Only gentle mixing on oily stocks with aqueous diluents is enough to make paclitaxel-contained emulsions. The optimum formulation contains oils from 1 to 3 wt%, Tween-80 and EPC from 0.4 to 1.2 wt%, respectively. Consequently, near 500 ppm of paclitaxel can be contained in emulsions. Moreover, these paclitaxel-containing emulsions are compatible with commonly used injection fluids. No precipitation is observed upon preparation of emulsion from dilution of oily stocks. Negligible cytotoxicity on these emulsions assessed with NIH/3T3 cells implied their good biocompatibility and promising applications as drug delivery carriers.
Lo
Jen-Ting
JT
Department of Chemical Engineering, National Cheng Kung University, Tainan 70101, Taiwan.
Chen
Bing-Hung
BH
Lee
Tzer-Min
TM
Han
Jun
J
Li
Jing-Liang
JL
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D001672:Biocompatible Materials / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions; D007928:Lethal Dose 50; D008055:Lipids / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D013501:Surface-Active Agents; D017239:Paclitaxel