Methods for producing chemoembolic agents for the delivery of anti-cancer agents
Described herein are chemoembolic compositions and agents. The compositions include one or more anti-cancer agents and a silk-elastinlike protein polymer, wherein the compositions are liquids prior to administration to a subject but convert to hydrogels upon administration to the subject. Administration of the Chemoembolic compositions to tumor and/or tumor vasculature in a subject having cancer can result in reduced or inhibited blood flow to the tumor as well as localized, sustained release of the anti-cancer agent in the vicinity of the tumor. Reduction in blood flow, in turn, results in a reduction of tumor volume and/or inhibition of tumor growth, while localized release of the anti-cancer agent results in reduced systemic effects and lower overall toxicity of treatment with the compositions.
1 . A method for producing a chemoembolic agent comprising admixing one or more anti-cancer agents with a sheared silk-elastinlike protein, wherein the silk-elastinlike protein is SELP-pSE8Y, SELP-pS2E8Y, SELP-pS4E8Y, or any combination thereof.
2 . The method of claim 1 , wherein the silk-elastinlike protein comprises one or more matrix metalloproteinase (MMP) cleavage sites.
3 . The method of claim 2 , wherein the one or more matrix metalloproteinase (MMP) cleavage sites comprise a cleavage site of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, or any combination thereof.
4 . The method of claim 1 , wherein the anti-cancer agent is paclitaxel, docetaxel, gemcitabine, a platinate, doxorubicin, geldanamycin, epirubicin, 9-aminocamptothecin, sorafenib, or any combination thereof, and wherein the anti-cancer agent is a neutral compound or the pharmaceutically-acceptable salt thereof.
5 . The method of claim 1 , wherein the anti-cancer agent is the pharmaceutically-acceptable salt of doxorubicin and the pharmaceutically-acceptable salt of sorafenib.
6 . The method of claim 1 , wherein the anti-cancer agent is doxorubicin hydrochloride and sorafenib to sylate.
7 . The method of claim 1 , wherein the anti-cancer agent is admixed with a liquid composition of the silk-elastinlike protein, wherein the silk-elastinlike protein is from 2% to 20% w/w of the liquid composition.
8 . The method of claim 7 , wherein the silk-elastinlike protein is from 5% to 15% w/w of the liquid composition.
9 . The method of claim 7 , wherein the anti-cancer agent is admixed with the liquid composition as a solution comprising a solvent, wherein the solvent comprises water, dimethylsulfoxide, or a combination thereof.
10 . The method of claim 1 , wherein the anti-cancer agent is from 1 mg/mL to 100 mg/mL of the chemoembolic agent.
11 . The method of claim 1 , wherein the anti-cancer drug is the pharmaceutically-acceptable salt of doxorubicin and the pharmaceutically-acceptable salt of sorafenib.
12 . The method of claim 1 , wherein the chemoembolic agent further comprises a contrast agent.
13 . The method of claim 1 , wherein the chemoembolic agent has a viscosity of less than equal to 700 cP at 18 to 23.degree. C.
14 . A chemoembolic agent produced by the method of claim 1 .
15 . A method for delivering an anti-cancer agent to a subject comprising administering the chemoembolic agent of claim 1 into the tumor vasculature of the subject.
16 . A method for treating cancer in a subject comprising administering the chemoembolic agent of claim 1 to the subject.
17 . A method for reducing or inhibiting the growth of a tumor in a subject comprising administering the chemoembolic agent of claim 1 into the tumor vasculature of the subject.
18 . A method of creating an embolism in tumor vasculature comprising administering a composition comprising a sheared silk-elastinlike protein into the tumor vasculature of the subject, wherein the silk-elastinlike protein is SELP-pSE8Y, SELP-pS2E8Y, SELP-pS4E8Y, or any combination thereof.
19 . A method of reducing blood flow to a tumor in a subject comprising administering a composition comprising a sheared silk-elastinlike protein into tumor vasculature of the subject, wherein the silk-elastinlike protein is SELP-pSE8Y, SELP-pS2E8Y, SELP-pS4E8Y, or any combination thereof.