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 election 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.
