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 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 particles without any polymeric matrix therein.

대표청구항 ▼

1. A drug delivery system comprising particles of a solid or liquid, substantially water insoluble pharmacologically active agent, coated with protein, wherein said protein coating has free protein associated therewith, wherein a portion of said pharmacologically active agent is contained withi

1. A drug delivery system comprising particles of a solid or liquid, substantially water insoluble pharmacologically active agent, coated with protein, wherein said protein coating has free protein associated therewith, wherein a portion of said pharmacologically active agent is contained within said protein coating and a portion of said pharmacologically active agent is associated with said free protein, and wherein the average diameter of said particles is no greater than about 1 micron. 2. A drug delivery system according to claim 1 wherein the average diameter of said particles is less than 200 nm.3. A drug delivery system according to claim 2 wherein said system is sterile filtered.4. A drug delivery system according to claim 1 wherein said particles are amorphous, crystalline, or a mixture thereof.5. A drug delivery system according to claim 4 wherein said particles are substantially amorphous.6. A drug delivery system according to claim 1 wherein said particles are suspended in a biocompatible aqueous liquid.7. Bioprotected particles of a substantially water insoluble pharmacologically active agent coated with protein, wherein said particles are surrounded by free protein associated therewith, wherein a portion of said pharmacologically active agent is contained within said protein coating and a portion of said pharmacologically active agent is associated with said free protein surrounding said protein coating, and wherein the average diameter of said particles is no greater than about 1 micron. 8. Bioprotected particles according to claim 7 wherein the average diameter of said particles is less than 200 nm.9. Bioprotected particles according to claim 8 wherein said particles are sterile filtered.10. Bioprotected particles according to claim 7 wherein said particles are amorphous, crystalline, or a mixture thereof.11. Bioprotected particles according to claim 10 wherein said particles are substantially amorphous.12. Bioprotected particles according to claim 7 wherein said pharmacologically active agent is paclitaxel and said protein is albumin.13. A drug delivery system according to claim 1 wherein said pharmacologically active agent is selected from the group consisting of an anti-neoplastic, an anesthetic and a hormone.14. A drug delivery system according to claim 13 wherein said anti-neoplastic is a taxane.15. A drug delivery system according to claim 13 wherein said anesthetic is propofol.16. A drug delivery system according to claim 13 wherein said hormone is a thyroid hormone.17. A drug delivery system according to claim 1 wherein said pharmacologically active agent is non-crystalline.18. The bioprotected particles according to claim 7 wherein said pharmacologically active agent is selected from the group consisting of an anti-neoplastic, an anesthetic and a hormone.19. The bioprotected particles according to claim 18 wherein said anti-neoplastic is a taxane.20. The bioprotected particles according to claim 18 wherein said anesthetic is propofol.21. The bioprotected particles according to claim 18 wherein said hormone is a thyroid hormone.