Activated nitric oxide donors and methods of making and using thereof
Described herein are compositions useful in anticancer treatment and prevention. The compositions are composed of (a) an O 2 -aryl substituted diazeniumdiolate and (b) an amphiphile, wherein the amount of amphiphile is sufficient to produce a liposome or micelle. The compositions described herein provide numerous advantages such as increased solubility and stability of the O 2 -aryl substituted diazeniumdiolate in vivo. The compositions also do not induce hypotension. Methods for using the compositions in anticancer treatment and prevention are also described herein.
1. A composition produced by the process comprising admixing
(a) O 2 -(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) or the pharmaceutically acceptable salt or ester thereof; and
(b) a poloxamer having the formula
HO(C 2 H 4 O) b (C 3 H 6 O) a (C 2 H 4 O) b H
wherein a is from 50 to 80 and b is from 10 to 25,
wherein the amount of poloxamer is sufficient to produce a micelle.
2. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable carrier.
3. The composition of claim 1 , wherein a is from 50 to 70.
4. The composition of claim 1 , wherein the amount of JS-K is less than 0.98% by weight of the micelle.
5. The composition of claim 1 , wherein the amount of JS-K is less than 0.52% by weight of the micelle.