Methods for improving the therapeutic index for a chemotherapeutic drug
This disclosure relates to methods for improving the therapeutic index of a chemotherapeutic drug in the treatment of patients afflicted with cancer, including, for example, reducing chemotherapy-related toxicity (e.g., liver toxicity).
1. A method for increasing the in vivo therapeutic index of a chemotherapeutic drug targeting aberrant mammalian cells, which method comprises:
a) combining a therapeutically effective amount of said drug with a biocompatible protein carrier;
b) forming a complex with said carrier and an effective amount of binding agent having specificity to said aberrant cells, wherein said binding agent populates the surface of said complex and retains specificity and further wherein said binding agent has a carrier protein-binding portion, and wherein said binding agent is hydrophobically bound to said complex; and
c) administering said complex to a patient, wherein said administration enhances delivery of said drug to said cells and reduces one or more side effects of said drug, thereby increasing the therapeutic index of said drug.
2. The method of claim 1 , wherein the binding agent is selected from the group consisting of aptamer, antibody, fusion protein, and Fc receptor.
3. The method of claim 1 , wherein the aberrant mammalian cells are selected from the group consisting of cancer cells, virus-infected cells, and bacteria-infected cells.
4. The method of claim 1 , wherein the protein carrier is selected from the group consisting of albumin, gelatin, elastin, gliadin, legumin, zein, soy protein, milk protein, and whey protein.
5. The method of claim 4 , wherein the protein carrier is albumin.
6. The method of claim 5 , wherein the complex further comprises an effective amount of paclitaxel to form said complex.
7. The method of claim 6 , wherein the amount of paclitaxel is between 0.1 mg/m 2 and 50 mg/m 2 .
8. The method of claim 1 , wherein said complex is less than 1 micron in diameter.