Isoflavonoid compositions and methods for the treatment of cancer
Provided herein is a pharmaceutical composition comprising an isoflavonoid derivative and a cyclodextrin. Also provided herein are methods of treating cancer, sensitizing cancer cells, and inducing apoptosis in cancer cells by administering such compositions. In specific instances, provided herein are intravenous compositions and therapies.
1. A pharmaceutical composition comprising: i) d-cis-3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)-8-methylchroman-7-ol provided in at least 90% enantiomeric excess and ii) a cyclodextrin.
2. The pharmaceutical composition of claim 1 , wherein the cyclodextrin is selected from the group consisting of SAE-CD derivatives, SBE-α-CD, SBE-β-CD, SBE1-β-CD, SBE4-β-CD, SBE7-β-CD, SBE-γ-CD, hydroxypropyl-β-cyclodextrin, 2-HP-β-CD, hydroxyethyl-β-cyclodextrin, hydroxypropyl-γ-cyclodextrin, hydroxyethyl-γ-cyclodextrin, dihydroxypropyl-β-cyclodextrin, glucosyl-α-cyclodextrin, glucosyl-β-cyclodextrin, diglucosyl-β-cyclodextrin, maltosyl-α-cyclodextrin, maltosyl-β-cyclodextrin, maltosyl-γ-cyclodextrin, maltotriosyl-β-cyclodextrin, maltotriosyl-γ-cyclodextrin, dimaltosyl-β-cyclodextrin, methyl-β-cyclodextrin, and derivatives and/or combinations thereof.
3. The pharmaceutical composition of claim 1 , wherein the cyclodextrin is SBE7-β-CD.
4. The pharmaceutical composition of claim 1 , wherein the cyclodextrin has a concentration (w/v) ranging from about 0.001% to about 50%.
5. The pharmaceutical composition of claim 1 , wherein the composition further comprises water.
6. The pharmaceutical composition of claim 1 , wherein the composition further comprises one or more of lactose, dextrose, mannitol, a pH buffering agent, an antioxidant agent, a preservative agent, a tonicity adjuster, or a combination thereof.
7. The pharmaceutical composition of claim 1 , wherein the composition comprises d-cis-3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)-8-methylchroman-7-ol in an amount of about 0.2-50 mg/mL.
8. A method of treating cancer in an individual in need of cancer therapy, the method comprising administering to the individual a pharmaceutical composition comprising: —i) d-cis-3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)-8-methylchroman-7-ol provided in at least 90% enantiomeric excess and —ii) a cyclodextrin.
9. The method of claim 7 , wherein the pharmaceutical composition increases or induces sensitivity of the cancer to a chemotherapeutic agent, anti-cancer agent, or radiation therapy.
10. The method of claim 7 , wherein the cancer has lost sensitivity to a chemotherapeutic agent, anti-cancer agent, or radiation therapy.
11. The method of claim 7 , wherein the cancer is selected from the group consisting of bladder cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, leukemia, lung cancer, melanoma, non-Hodgkin lymphoma, ovarian cancer, pancreatic cancer, prostate cancer, thyroid cancer, and cancers of the brain.
12. The method of claim 7 , wherein the cancer is human breast cancer or ovarian cancer.