COMPOSITIONS AND METHODS FOR THE TREATMENT OF BLADDER CANCER
Compositions and methods for the treatment of bladder cancer include intravesical dosage forms of a neoplastic agent and a permeation enhancer. The neoplastic agent may be valrubicin. Pharmaceutical compositions include intravesical dosage forms of a neoplastic agent complexed liposomes. Tight junction openers may be used for the effective delivery of the neoplastic agent.
1 . A pharmaceutical composition comprising an effective amount of valrubicin and dimethyl sulfoxide in an intravesical dosage form.
2 . The pharmaceutical composition of claim 1 , wherein the effective amount of valrubicin is from about 5 mg/mL to about 100 mg/mL, from about 10 mg/mL to about 90 mg/mL, from about 15 mg/mL to about 80 mg/mL, from about 20 mg/mL to about 70 mg/mL, from about 25 mg/mL to about 70 mg/mL, from about 30 mg/mL to about 60 mg/mL, from about 35 mg/mL to about 50 mg/mL, or from about 35 mg/mL to about 45 mg/mL.
3 . The pharmaceutical composition of claim 1 comprising one or more additional chemical permeation enhancers selected from the group consisting of: ethanol, isopropanol, dimethylacetamide, dimethylformamide, decylmethylsulfoxide, 2-pyrrolidone, N-ethyl-2-pyrrolidone, capric acid, linoleic acid, ureas, sodium dodecyl sulfate, sodium lauryl sulfate, and mixtures of any two or more thereof.
4 . The pharmaceutical composition of claim 1 , wherein the effective amount of valrubicin and dimethyl sulfoxide is sufficient to treat bladder cancer.
5 . The pharmaceutical composition of claim 1 comprising a junction opener.
6 . The pharmaceutical composition of claim 5 , wherein the junction opener is selected from the group consisting of: trimethyl-chitosan, mono-N-carboxymethyl chitosan, N-diethyl methyl chitosan, sodium caprate, cytochalasin B, IL-1, polycarbophil, carbopol 934P, N-sulfato-N,O-carboxymethylchitosan, Zounla occludens toxin, 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine, and mixtures of any two or more thereof.
7 . The pharmaceutical composition of claim 5 , wherein the amount of the junction opener is from about 1 to about 15 percent by weight/volume of the dosage form.
8 . The pharmaceutical composition of claim 1 comprising a polyethoxylated castor oil.
9 . The pharmaceutical composition of claim 8 , wherein the polyethoxylated castor oil is Cremophor.
10 . The pharmaceutical composition of claim 9 , wherein the Cremophor and dimethyl sulfoxide are provided in equal amounts.
11 . The pharmaceutical composition of claim 1 further comprising a mucin-degrading compound.
12 . The pharmaceutical composition of claim 11 , wherein the mucin-degrading compound is selected from the group consisting of: trypsin, hyaluronidase, protamine sulfate, and norepinephrine.
13 . The pharmaceutical composition of claim 1 further comprising a bioadhesive or mucoadhesive agent.
14 . The pharmaceutical composition of claim 13 , wherein the mucoadhesive agent is polyacrylic acid.
15 . The pharmaceutical composition of claim 1 further comprising an ionic or non-ionic surfactant, a polyvinyl pyrrolidone, alginates, a polyacrylic acid, or a mixture of any two or more thereof.
16 . The pharmaceutical composition of claim 15 , wherein the ionic and non-ionic surfactants are polyoxyethylene castor oil derivatives, block copolymers of ethylene oxide and propylene oxide, sorbitan fatty acid esters, or a mixture of any two or more thereof.
17 . The pharmaceutical composition of claim 16 , wherein the polyacrylic acids are Carbomer 934P, Carbomer 940, Carbomer 941, Carbomer 974P, Carbomer 980, Carbomer 1342, polycarbophil, calcium polycarbophil, or a mixture of any two or more thereof.
18 . A pharmaceutical composition comprising an effective amount of valrubicin and 2-hydroxy-propyl-β-cyclodextran in an intravesical dosage form.
19 . A pharmaceutical composition comprising:
a liposomal dosage form comprising an effective amount of liposome-entrapped valrubicin;
wherein, the liposome comprises at least one liposome forming material selected from the group consisting of: phosphatidyl choline and phosphatidyl ethanolamine.
20 . A method for treating bladder cancer comprising administering the pharmaceutical composition of claim 1 .
21 . A method for treating bladder cancer comprising administering the pharmaceutical composition of claim 18 .
22 . A method for treating bladder cancer comprising administering the pharmaceutical composition of claim 19 .