In accordance with the present invention, there are provided compositions and methods 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,
protein and pharmacologically
active agent 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 about 1 micron. The use of specific composition 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 according to the invention 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 unique
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.