Nanoparticles Containing a Taxane and their Use

Abstract

Symmetrically and asymmetrically branched homopolymers are modified at the surface level with functional groups that enable forming aggregates with a taxane, such as, paclitaxel and derivatives thereof, which are water insoluble or poorly water soluble. The aggregates are formed by interaction of a taxane and a homopolymer. Such aggregates improve drug solubility, stability, delivery and efficacy.

What is claimed is: 
     
         1 . An aggregate comprising:
 a) a polyoxazoline comprising at least one first terminal group modified with a hydrophobic moiety, wherein said polyoxazoline further comprises a linear portion, a branched portion or both, said branched portion comprises a symmetrically branched polymer, an asymmetrically branched polymer or a combination thereof; and said polyoxazoline comprises a molar ratio of monomer to initiator in a range of from 50:1 to 80:1, and   b) a taxane,   wherein said aggregate comprises a weight ratio of polymer to taxane of 6:1 to 8:1; is from about 50 nm to about 100 nm in size; and comprises a filtration rate through a 0.22 μm filter of from 50 to 100%.   
     
     
         2 . The aggregate of  claim 1 , wherein said initiator comprises a hydrophobic electrophilic molecule. 
     
     
         3 . The aggregate of  claim 1 , wherein said initiator comprises a hydrocarbon. 
     
     
         4 . The aggregate of  claim 1 , wherein said initiator comprises an aliphatic hydrocarbon, an aromatic hydrocarbon or a combination of both. 
     
     
         5 . The aggregate of  claim 1 , wherein said initiator comprises a halide functional group. 
     
     
         6 . The aggregate of  claim 5 , wherein said initiator comprises an alkyl halide, an aralkyl halide, an acyl halide or combination thereof. 
     
     
         7 . The aggregate of  claim 3 , wherein said hydrocarbon comprises from 1 to about 22 carbons, which may be saturated or unsaturated. 
     
     
         8 . The aggregate of  claim 1 , wherein said initiator comprises methyl iodide, methyl bromide, methyl chloride, ethyl iodide, ethyl bromide, ethyl chloride, 1-iodopropane, 1-bromopropane, 1-chloropropane, 1-iodobutane, 1-bromobutane, 1-chlorobutane, 1-iodopentane, 1-bromopentane, 1-chloropentane, 1-iodo hexane, 1-bromo hexane, 1-chloro hexane, 1-iodo dodecane, 1-bromo dodecane, 1-chloro dodecane, 1-iodo octadodecane, 1-bromo octadodecane, 1-chloro octadodecane, benzyl iodide, benzyl bromide, benzyl chloride, allyl bromide, acyl iodide, acyl bromide, acyl chloride, benzoyl bromide, benzoyl chloride or a combination thereof. 
     
     
         9 . The aggregate of  claim 1 , wherein said initiator comprises a tosyl group. 
     
     
         10 . The aggregate of  claim 1 , comprising a size from 50 nm to about 100 nm before lyophilization. 
     
     
         11 . The aggregate of  claim 1 , wherein the polyoxazoline further comprises a second terminal group comprising a functional group modified by an ethylenediamine (EDA) or an ethylenediamine derivative thereof. 
     
     
         12 . The aggregate of  claim 11 , wherein said ethylenediamine derivative comprises diethylenetriamine, triethylenetetramine, tetraethylenepentamine, pentaethylenehexamine, polyethylene amine or tetramethylethylenediamine. 
     
     
         13 . The aggregate of  claim 1 , wherein said taxane is associated with said at least one first terminal group. 
     
     
         14 . The aggregate of  claim 1 , wherein said polyoxazoline comprises poly(2-oxazoline), poly(2-substituted oxazoline) or a combination thereof. 
     
     
         15 . The aggregate of  claim 1 , wherein said polyoxazoline comprises poly(2-methyloxazoline), poly(2-ethyloxazoline), poly(2-propyloxazoline) or poly(2-butyloxazoline) or a combination thereof. 
     
     
         16 . The aggregate of  claim 1 , further comprising a targeting moiety. 
     
     
         17 . The aggregate of  claim 16 , wherein said targeting moiety comprises an antibody, an antigen-binding portion thereof, an antigen, a cell surface receptor, a cytosolic receptor, a cell receptor ligand or a lectin ligand. 
     
     
         18 . The aggregate of  claim 1 , wherein said taxane comprises paclitaxel, docetaxel or a combination thereof. 
     
     
         19 . A pharmaceutical composition for treating a disease of a subject in need thereof, wherein said pharmaceutical composition comprises an aggregate comprising:
 a) a polyoxazoline comprising at least one first terminal group modified with a hydrophobic moiety, wherein said polyoxazoline further comprises a linear portion, a branched portion or both, said branched portion comprises a symmetrically branched polymer, an asymmetrically branched polymer or a combination thereof;   and said polyoxazoline comprises a molar ratio of monomer to initiator in a range of from 50:1 to 80:1, and   b) a taxane,   wherein said aggregate comprises a weight ratio of polymer to taxane of 6:1 to 8:1; is from about 50 nm to about 100 nm in size; and comprises a filtration rate through a 0.22 μm filter of from 50 to 100%.   
     
     
         20 . The pharmaceutical composition of  claim 19 , comprising a taxane for treating a breast cancer, an ovarian cancer, a lung cancer, NSCLC (Non-Small Cell Lung Cancer), a colon cancer, a gastric cancer, a melanoma, a head and neck cancer, a pancreatic cancer or a combination thereof.