초록 ▼

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 susp

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.

대표청구항 ▼

1. An emulsion comprising paclitaxel, the emulsion comprising a first phase comprising nanodroplets comprising paclitaxel dissolved in chloroform and a water miscible alcohol solvent for paclitaxel, wherein the concentration of the water miscible alcohol solvent in the first phase is about 5-25% (v/

1. An emulsion comprising paclitaxel, the emulsion comprising a first phase comprising nanodroplets comprising paclitaxel dissolved in chloroform and a water miscible alcohol solvent for paclitaxel, wherein the concentration of the water miscible alcohol solvent in the first phase is about 5-25% (v/v), anda second phase comprising water and albumin,wherein the emulsion is free of surfactants. 2. The emulsion of claim 1, wherein the water miscible alcohol solvent for paclitaxel is ethanol. 3. The emulsion of claim 1, wherein the albumin concentration in the emulsion is about 0.05% to 25% (w/v). 4. The emulsion of claim 3, wherein the albumin concentration in the emulsion is about 0.5% to 5%. 5. The emulsion of claim 2, wherein the chloroform to ethanol ratio in the emulsion is 9:1. 6. The emulsion of claim 1, wherein the phase fraction of the first phase in the emulsion is between about 0.5% and 15%. 7. The emulsion of claim 6, wherein the phase fraction of the first phase in the emulsion is between 1% and 8%. 8. The emulsion of claim 1, wherein the albumin is human albumin. 9. The emulsion of claim 2, wherein the albumin is human albumin. 10. The emulsion of claim 3, wherein the albumin is human albumin. 11. The emulsion of claim 4, wherein the albumin is human albumin. 12. The emulsion of claim 5, wherein the albumin is human albumin. 13. The emulsion of claim 6, wherein the albumin is human albumin. 14. The emulsion of claim 7, wherein the albumin is human albumin.