Vehicles for intravenous administration of paclitaxel having reduced toxicity

摘要

Compositions and methods are provided, useful for the in vivo delivery of substantially water insoluble pharmacologically active agents (such as the anticancer drug paclitaxel) in which the pharmacologically active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, proteins and pharmacologically active agents in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diameter of less than 1 micron. The use of specific compositions and preparation conditions (e.g., addition of a polar solvent to the organic phase) and careful selection of the proper organic phase and phase fraction enables the reproducible production of unusually small nanoparticles of less than 200 nm diameter, which can be sterile-filtered. The particulate system produced can be converted into a redispersible dry powder comprising nanoparticles of water-insoluble drug coated with a protein, and free protein to which molecules of the pharmacological agent are bound. This results in a delivery system, in which part of the pharmacologically active agent is readily bioavailable in the form of molecules bound to the protein, and part of the agent is present within particles without any polymeric matrix therein.