Compositions and devices incorporating water-insoluble therapeutic agents and methods of the use thereof
Various aspects of the present invention provide compositions and implantable devices including a water-insoluble therapeutic agent solubilized in a matrix of a gallate-containing compound. Other aspects provide methods of manufacturing and using such compositions and devices.
1. A composition comprising:
a cream, paste, or gel comprising a gallate containing compound and a drug, wherein the gallate containing compound is tannic acid.
2. The composition of claim 1 , wherein the drug is amphotericin.
3. The composition of claim 1 , comprising a cream comprising the gallate containing compound and the drug.
4. The composition of claim 1 , comprising a paste comprising the gallate containing compound and the drug.
5. The composition of claim 1 , wherein the gallate containing compound is present is an amount effective in increasing the cellular uptake of the drug.
6. The composition of claim 1 , wherein the gallate containing compound is present is an amount effective in increasing the solubility of the drug in an aqueous medium.
7. The composition of claim 1 , wherein the gallate containing compound and the drug are contained within a matrix of a polymeric microparticle, and wherein the drug is a water-insoluble therapeutic agent.
8. The composition of claim 7 , wherein the polymeric matrix comprises a biodegradable polymer.
9. The composition of claim 7 , wherein the polymeric matrix comprises a non-biodegradable polymer.
10. The composition of claim 7 , wherein the gallate containing compound and the water-insoluble therapeutic agent are present at a weight ratio of between 1 to 40 and 500 to 1 gallate containing compound to water-insoluble therapeutic agent.
11. A composition comprising:
an aqueous solvent;
a gallate containing compound; and
water-insoluble therapeutic agent,
wherein the gallate containing compound is tannic acid.
12. The composition of claim 11 , wherein the aqueous solvent is selected from the group consisting of saline and water.
13. The composition of claim 11 , wherein the gallate containing compound is present in an amount that increases the solubility of a water-insoluble therapeutic agent in the composition by 10, 20, 30, 40, 50 75, 100, 125, 150, 200, 300 or 400 percentage compared to an otherwise identical composition that does not include the gallate containing compound.
14. The composition of claim 11 , wherein the water-insoluble therapeutic agent is selected from the group consisting of paclitaxel, docetaxel, a paclitaxel analog, or a paclitaxel derivative or other taxane compound; a macrolide immunosuppressive agent, sirolimus, pimecrolimus, tacrolimus, everolimus, zotarolimus, novolimus, myolimus, temsirolimus, deforolimus, or biolimus; an antiproliferative agent; a smooth muscle cell inhibitor; and an inhibitor of the mammalian target of rapamycin (mTOR inhibitor).
15. The composition of claim 11 , wherein the water-insoluble therapeutic agent is selected from the group consisting of antiproliferative agents immunosuppressive agents, restenosis-inhibiting agents, anti-cancer agents, analgesics/antipyretics, anesthetics, antiasthmatics, antibiotics, antidepressants, antidiabetics, antifungal agents, antihypertensive agents, anti-inflammatories, antineoplastics, antianxiety agents, sedatives/hypnotics, antianginal agents, nitrates, antipsychotic agents, antimanic agents, antiarrhythmics, antiarthritic agents, antigout agents, thrombolytic agents, hemorheologic agents, anticonvulsants, antihistamines, agents useful for calcium regulation, antibacterial agents, antiviral agents, antimicrobials, anti-infectives, bronchodilators, steroids and hormones.
16. The composition of claim 1 , wherein the drug is selected from the group consisting of paclitaxel, docetaxel, a paclitaxel analog, or a paclitaxel derivative or other taxane compound; a macrolide immunosuppressive agent, sirolimus, pimecrolimus, tacrolimus, everolimus, zotarolimus, novolimus, myolimus, temsirolimus, deforolimus, biolimus, an antiproliferative agent; a smooth muscle cell inhibitor; and an inhibitor of the mammalian target of rapamycin (mTOR inhibitor).
17. The composition of claim 16 , wherein the drug is paclitaxel.
18. The composition of claim 16 , wherein the drug is selected from the group consisting of sirolimus, pimecrolimus, tacrolimus, everolimus, zotarolimus, novolimus, myolimus, temsirolimus, deforolimus, and biolimus.
19. The composition of claim 18 , wherein the drug is sirolimus.