Delivery of drug nanoparticles and methods of use thereof

Abstract

A hydrophobic topical skin composition is disclosed. The composition includes greater than 50% w/w of the composition of a continuous hydrophobic carrier, 5-24% w/w of one or more volatile silicone fluids, and 0.1 to 5% w/w of the composition of a plurality of taxane nanoparticles, wherein the mean particle size (number) of the taxane nanoparticles is from 0.1 microns to 1.5 microns, and wherein the taxane nanoparticles are crystalline nanoparticles or a combination of amorphous and crystalline nanoparticles.

1 .- 25 . (canceled) 
     
     
         26 . An aqueous based composition comprising:
 (a) a plurality of taxane nanoparticles; and   (b) an aqueous carrier comprising:
 (i) poloxamer 407; and 
 (ii) a quaternary ammonium compound or a cross-linked acrylic acid polymer, or a combination thereof; 
   wherein the plurality of taxane nanoparticles are dispersed in the aqueous carrier,   wherein the initial mean particle size (number) of the taxane nanoparticles is from 0.1 microns to 1.5 microns, and   wherein the mean particle size of the taxane nanoparticles does not grow larger than 20% of the initial mean particle size when the composition is stored at room temperature for at least 6 months.   
     
     
         27 . The composition of  claim 26 , wherein the taxane nanoparticles are crystalline. 
     
     
         28 . The composition of  claim 26 , wherein the taxane nanoparticles are paclitaxel nanoparticles, docetaxel nanoparticles, or cabazitaxel nanoparticles. 
     
     
         29 . The composition of  claim 26 , wherein the quaternary ammonium compound is selected from benzalkonium chloride or benzethonium chloride. 
     
     
         30 . The composition of  claim 26 , wherein the cross-linked acrylic acid polymer is selected from a carbomer, an acrylates copolymer, an acrylates/C10-30 alkyl acrylate crosspolymer, an acrylates crosspolymer-4, or a polyacrylate-1 crosspolymer. 
     
     
         31 . The composition of  claim 26 , wherein the concentration of the quaternary ammonium compound is at least 1% w/w. 
     
     
         32 . The composition of  claim 26 , wherein the concentration of the cross-linked acrylic acid polymer is at least 0.5% w/w. 
     
     
         33 . The composition of  claim 26 , wherein the concentration of the poloxamer 407 is at least 2% w/w. 
     
     
         34 . A method of inhibiting the crystal growth of crystalline taxane nanoparticles, the method comprising:
 (a) providing crystalline taxane nanoparticles to an aqueous based carrier to form a dispersion; and   (b) adding poloxamer 407 and a quaternary ammonium compound or a cross-linked acrylic acid polymer, or a combination thereof, to the dispersion or to the aqueous based carrier before the dispersion is formed,   wherein the initial mean particle size (number) of the crystalline taxane nanoparticles is from 0.1 microns to 1.5 microns.   
     
     
         35 . The method of  claim 34 , wherein the crystalline taxane nanoparticles do not grow larger than 20% of the initial mean particle size when the composition is stored at room temperature for at least 6 months. 
     
     
         36 . The composition of  claim 34 , wherein the crystalline taxane nanoparticles are paclitaxel nanoparticles, docetaxel nanoparticles, or cabazitaxel nanoparticles. 
     
     
         37 . The composition of  claim 34 , wherein the quaternary ammonium compound is selected from benzalkonium chloride and/or benzethonium chloride. 
     
     
         38 . The composition of  claim 34 , wherein the cross-linked acrylic acid polymer is selected from a carbomer, an acrylates copolymer, an acrylates/C10-30 alkyl acrylate crosspolymer, an acrylates crosspolymer-4, or a polyacrylate-1 crosspolymer. 
     
     
         39 . The composition of  claim 34 , wherein the concentration of the quaternary ammonium compound is at least 1% w/w. 
     
     
         40 . The composition of  claim 34 , wherein the concentration of the cross-linked acrylic acid polymer is at least 0.5% w/w. 
     
     
         41 . The composition of  claim 34 , wherein the concentration of the poloxamer 407 is at least 2% w/w.