A mixed micellar formulation suitable for the parenteral administration of taxol.
Taxol is a promising antitumor agent with poor water solubility. Intravenous administration of a current taxol formulation in a non-aqueous vehicle containing Cremophor EL may cause allergic reactions and precipitation upon aqueous dilution. In this study a novel approach to formulate taxol in aqueous medium for i.v. delivery is described. The drug is solubilized in bile salt (BS)/phospholipid (PC) mixed micelles. The solubilization potential of the mixed micelles increased as the total lipid concentration and the molar ratio of PC/BS increased. Precipitation of the drug upon dilution was avoided by the spontaneous formation of drug-loaded liposomes from mixed micelles. The formulation can be stored in a freeze-dried form as mixed micelles to achieve optimum stability, and liposomes can be prepared by simple dilution just before administration. As judged by a panel of cultured cell lines, the cytotoxic activity of taxol was retained when formulated as a mixed-micellar solution. Further, for the same solubilization potential, the mixed-micellar vehicle appeared to be less toxic than the standard nonaqueous vehicle of taxol containing Cremophor EL.
Alkan-Onyuksel
H
H
Department of Pharmaceutics and Pharmacodynamics, College of Pharmacy, University of Illinois at Chicago 60612.
Ramakrishnan
S
S
Chai
H B
HB
Pezzuto
J M
JM
D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004337:Drug Carriers; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D008081:Liposomes; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D010743:Phospholipids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000633:toxicity; D012995:Solubility; D014407:Tumor Cells, Cultured
D001647:Bile Acids and Salts; D004337:Drug Carriers; D008081:Liposomes; D008823:Micelles; D010743:Phospholipids; C022131:cremophor; D011092:Polyethylene Glycols; D017239:Paclitaxel