Protein stabilized pharmacologically active agents, methods for the preparation thereof, and methods for the use thereof.


In accordance with the present invention, there are provided compns. and methods useful for the in vivo delivery of substantially water insol. pharmacol. active agents (such as the anticancer drug paclitaxel) in which the pharmacol. active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacol. 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 diam. of less than about 1 μ. The use of specific compn. and prepn. conditions (e.g., addn. of a polar solvent to the org. phase), and careful election of the proper org. phase and phase fraction, enables the reproducible prodn. of unusually small nanoparticles of less than 200 nm diam., 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-insol. drug coated with a protein, and free protein to which mols. of the pharmacol. agent are bound. This results in a unique delivery system, in which part of the pharmacol. active agent is readily bioavailable (in the form of mols. bound to the protein), and part of the agent is present within particles without any polymeric matrix therein. [on SciFinder(R)]


CAPLUS AN 2004:485154(Patent)