DESAI, NEIL P.,SOON-SHIONG, PATRICK,MAGDASSI, SHLOMO,SAHADEVAN, DAVID C.
申请号：
CA2294981
公开号：
CA2294981C
申请日:
1998.06.26
申请国别(地区):
CA
年份:
2012
代理人:
摘要：
In accordance with the present invention, there are provided compositions andmethods useful for the in vivo delivery of substantially water insolublepharmacologically active agents (such as the anticancer drug paclitaxel) inwhich the pharmacologically active agent is delivered in the form of suspendedparticles coated with protein (which acts as a stabilizing agent). Inparticular, protein and pharmacologically active agent in a biocompatibledispersing medium are subjected to high shear, in the absence of anyconventional surfactants, and also in the absence of any polymeric corematerial for the particles. The procedure yields particles with a diameter ofless than about 1 micron. The use of specific composition and preparationconditions (e.g., addition of a polar solvent to the organic phase), andcareful selection of the proper organic phase and phase fraction, enables thereproducible production of unusually small nanoparticles of less than 200 nmdiameter, which can be sterile-filtered. The particulate system producedaccording to the invention can be converted into a redispersible dry powdercomprising nanoparticles of water-insoluble drug coated with a protein, andfree protein to which molecules of the pharmacological agent are bound. Thisresults in a unique delivery system, in which part of the pharmacologicallyactive agent is readily bioavailable (in the form of molecules bound to theprotein), and part of the agent is present within particles without anypolymeric matrix therein.
