Injectable diethylstilbestrol nanosuspension formulation

Abstract

Embodiments of the present disclosure pertain to formulations for cancer treatment that include a particle loaded with diethylstilbestrol (DES) and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may also be loaded into the particle. The formulations may also include a stabilizer that is also loaded into the particle. The particles may be dispersed in an aqueous solution to form a nanosuspension that is adapted for subcutaneous administration and sustained release of DES. Additional embodiments pertain to methods of treating cancer in a subject by administering to the subject a formulation of the present disclosure. The subject may be a human suffering from prostate cancer. The administration of the formulations to the subject may bypass or minimize first pass metabolism. The administration may also minimize hepatic exposure of DES. Additional embodiments pertain to methods of making the formulations of the present disclosure by loading a particle with DES.

What is claimed is: 
     
         1 . A formulation for cancer treatment comprising:
 a particle loaded with diethylstilbestrol; and   a pharmaceutically acceptable carrier.   
     
     
         2 . The formulation of  claim 1 , wherein the particle encapsulates diethylstilbestrol. 
     
     
         3 . The formulation of  claim 1 , wherein the particle is selected from the group consisting of glass-based particles, metal-based particles, lipid-based particles, liposomes, carbon-based particles, polymer-based particles, silica-based particles, and combinations thereof. 
     
     
         4 . The formulation of  claim 1 , wherein the particle comprises glass-based particles or metal-based particles. 
     
     
         5 . The formulation of  claim 1 , wherein the particle has a size of less than about 1,000 nm in diameter. 
     
     
         6 . The formulation of  claim 1 , wherein the particle has a size ranging from about 100 nm to about 500 nm in diameter. 
     
     
         7 . The formulation of  claim 1 , wherein the pharmaceutically acceptable carrier is loaded into the particle. 
     
     
         8 . The formulation of  claim 1 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of excipients, solvents, fillers, binders, disintegrants, lubricants, buffers, oils, and combinations thereof. 
     
     
         9 . The formulation of  claim 1 , wherein the diethylstilbestrol is in solid state. 
     
     
         10 . The formulation of  claim 1 , wherein the formulation further comprises a stabilizer. 
     
     
         11 . The formulation of  claim 10 , wherein the stabilizer is loaded into the particle. 
     
     
         12 . The formulation of  claim 10 , wherein the stabilizer is selected from the group consisting of surfactants, anti-oxidants, antifoaming agents, wetting agents, dispersants, thickeners, emulsifiers, binders, and combinations thereof. 
     
     
         13 . The formulation of  claim 10 , wherein the stabilizer is present in a concentration ranging from about 5 wt % to about 15 wt %. 
     
     
         14 . The formulation of  claim 1 , wherein the cancer is prostate cancer. 
     
     
         15 . The formulation of  claim 1 , further comprising one or more additional therapeutic agents, wherein the one or more additional therapeutic agents are suitable for the treatment of cancer. 
     
     
         16 . The formulation of  claim 1 , wherein the particle is dispersed in an aqueous solution. 
     
     
         17 . The formulation of  claim 1 , wherein the formulation is adapted for subcutaneous administration and sustained release of diethylstilbestrol from the particles. 
     
     
         18 . A method of treating cancer in a subject in need thereof, comprising:
 administering to the subject a formulation, wherein the formulation comprises:
 a particle loaded with diethylstilbestrol; and 
 a pharmaceutically acceptable carrier. 
   
     
     
         19 . The method of  claim 18 , wherein the subject is a human being. 
     
     
         20 . The method of  claim 18 , wherein the cancer is prostate cancer. 
     
     
         21 . The method of  claim 18 , wherein the administering occurs in a manner that bypasses or minimizes first pass metabolism. 
     
     
         22 . The method of  claim 18 , wherein the administering occurs in a manner that minimizes hepatic exposure of diethylstilbestrol. 
     
     
         23 . The method of  claim 22 , wherein the administering minimizes hepatic exposure of diethylstilbestrol by maintaining the liver-to-plasma diethylstilbestrol concentration ratio to less than 2 after 24 hours of administration. 
     
     
         24 . The method of  claim 22 , wherein the administering minimizes hepatic exposure of diethylstilbestrol by maintaining the liver-to-plasma diethylstilbestrol concentration ratio to less than 0.5 after 24 hours of administration. 
     
     
         25 . The method of  claim 18 , wherein the administering occurs through non-oral routes of administration. 
     
     
         26 . The method of  claim 25 , wherein the non-oral routes of administration are selected from the group consisting of inhalation, subcutaneous administration, intravenous administration, intraperitoneal administration, intramuscular administration, intrathecal injection, topical administration, central administration, peripheral administration, and combinations thereof. 
     
     
         27 . The method of  claim 25 , wherein the administering comprises subcutaneous administration. 
     
     
         28 . The method of  claim 18 , wherein the particle encapsulates diethylstilbestrol. 
     
     
         29 . The method of  claim 18 , wherein the particle is selected from the group consisting of glass-based particles, metal-based particles, lipid-based particles, liposomes, carbon-based particles, polymer-based particles, silica-based particles, and combinations thereof. 
     
     
         30 . The method of  claim 18 , wherein the particle has a size of less than about 1,000 nm in diameter. 
     
     
         31 . The method of  claim 18 , wherein the particle has a size ranging from about 100 nm to about 500 nm in diameter. 
     
     
         32 . The method of  claim 18 , wherein the pharmaceutically acceptable carrier is loaded into the particle. 
     
     
         33 . The method of  claim 18 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of excipients, solvents, fillers, binders, disintegrants, lubricants, buffers, oils, and combinations thereof. 
     
     
         34 . The method of  claim 18 , wherein the formulation further comprises a stabilizer. 
     
     
         35 . The method of  claim 34 , wherein the stabilizer is loaded into the particle. 
     
     
         36 . The method of  claim 34 , wherein the stabilizer is present in a concentration ranging from about 5 wt % to about 15 wt %. 
     
     
         37 . The method of  claim 18 , wherein the formulation further comprises one or more additional therapeutic agents, wherein the one or more additional therapeutic agents are suitable for the treatment of cancer. 
     
     
         38 . The method of  claim 18 , wherein the particle is dispersed in an aqueous solution. 
     
     
         39 . A method of making a formulation for cancer treatment comprising:
 loading a particle with diethylstilbestrol.   
     
     
         40 . The method of  claim 39 , wherein the loading occurs by a method selected from the group consisting of media milling, wet milling, stirring, high pressure homogenization, and combinations thereof. 
     
     
         41 . The method of  claim 39 , wherein the loading enhances the solubility of diethylstilbestrol. 
     
     
         42 . The method of  claim 39 , wherein the loading occurs in the presence of a stabilizer, and wherein the stabilizer gets loaded into the particle. 
     
     
         43 . The method of  claim 39 , wherein the loading occurs in the presence of a pharmaceutically acceptable carrier, and wherein the pharmaceutically acceptable carrier gets loaded into the particle.