Delivering enzyme using an injectable hydrogel depot

Abstract

Compositions and methods for delivering enzymes in enzyme hydrogel formulations are disclosed. More particularly, the present disclosure relates to injectable enzyme hydrogel formulations and delivery of injectable enzyme hydrogel formulations. Also disclosed are methods for GALNS enzyme replacement therapy and lysosomal enzyme replacement therapy.

What is claimed is: 
     
         1 . A method of administering to an individual in need thereof an enzyme replacement therapy in an injectable enzyme hydrogel formulation, wherein the injectable enzyme hydrogel formulation is not a microparticle, the method comprising:
 preparing an injectable enzyme hydrogel formulation by mixing an enzyme, a polymer, and a buffer solution to form a precursor solution;   initiating polymerization of the precursor solution to form the injectable enzyme hydrogel formulation; and   administering the enzyme hydrogel formulation to the individual in need thereof.   
     
     
         2 . The method of  claim 1 , further comprising monitoring polymerization of the injectable enzyme hydrogel formulation. 
     
     
         3 . The method of  claim 1 , further comprising introducing the injectable enzyme hydrogel formulation into an applicator. 
     
     
         4 . The method of  claim 1 , wherein the enzyme is selected from the group consisting of N-acetylgalactosamine 6-sulfate sulfatase (GALNS) and a lysosomal enzyme selected from the group consisting of Iduronate-2-sulfate sulfatase, Heparan N sulfatase, N-acetylglucosaminidase, acetyl-CoA: glucosaminide acetyltransferase, N-acetylglucosamine 6-sulfatase, Arylsulfatase B, Glucuronidase, acid glucosidase, and combinations thereof. 
     
     
         5 . The method of  claim 1 , wherein the enzyme comprises a recombinant enzyme. 
     
     
         6 . The method of  claim 1 , wherein the enzyme comprises a human enzyme. 
     
     
         7 . The method of  claim 1 , wherein the polymer comprises polyethylene glycol (PEG), polyethylene glycol acrylate (PEGAc), poly(glycolic acid) (PGA), poly(L-lactic acid) (PLA), poly(lactide-co-glycolide) (PLGA), poly(L-lactide) (PLLA), poly(D,L-lactide) (p(DLLA)), poly(ethylene glycol)1-co-poly(L-lactide) (PEG-PLLA), poly(ε-caprolactone (PCL), poly(L-lactide-co-ε-caprolactone) (P(LLA-CL)), poly(ε-caprolactone-co-ethyl ethylene phosphate (P(CL-EEP)), poly(ethylene-co-vinyl alcohol), poly(ethylenimine), polymethylmethacrylate (PMMA), hyaluronic acid, chitosan, pluronics, polyacrylamide, poly(vinyl alcohol) (PVA), polyhydroxyethylmethacrylate (polyHEMA), and combinations thereof. 
     
     
         8 . The method of  claim 1 , wherein the polymer is selected from the group consisting of 3-arm polyethylene glycol acrylate, 4-arm polyethylene glycol acrylate, 6-arm polyethylene glycol acrylate, 8-arm polyethylene glycol acrylate, and combinations thereof. 
     
     
         9 . The method of  claim 8 , wherein the polymer is 4-arm polyethylene glycol acrylate. 
     
     
         10 . The method of  claim 1 , wherein the buffer comprises water, HEPES, phosphate buffered saline, tris buffered saline, and combinations thereof. 
     
     
         11 . A method of treating Mucopolysaccharidoses (MPS) in an individual having Mucopolysaccharidoses, the method comprising:
 administering to the individual an injectable N-acetylgalactosamine 6-sulfate sulfatase (GALNS) enzyme replacement therapy, wherein the GALNS enzyme replacement therapy comprises an injectable GALNS hydrogel composition comprising GALNS, a polymer, and a buffer, wherein the enzyme hydrogel formulation is not a microparticle.   
     
     
         12 . The method of  claim 11 , wherein the GALNS is a recombinant human GALNS. 
     
     
         13 . The method of  claim 11 , wherein the GALNS dosage ranges from about 100 Units/g/week to about 1000 Units/g/week. 
     
     
         14 . The method of  claim 11 , wherein 0.5 mg/kg of body weight per week (mg/kg/week) to about 4 mg/kg of body weight per week (mg/kg/week). 
     
     
         15 . The method of  claim 11 , wherein the polymer comprises polyethylene glycol (PEG), polyethylene glycol acrylate (PEGAc), poly(glycolic acid) (PGA), poly(L-lactic acid) (PLA), poly(lactide-co-glycolide) (PLGA), poly(L-lactide) (PLLA), poly(D,L-lactide) (p(DLLA)), poly(ethylene glycol)1-co-poly(L-lactide) (PEG-PLLA), poly(ε-caprolactone (PCL), poly(L-lactide-co-ε-caprolactone) (P(LLA-CL)), poly(ε-caprolactone-co-ethyl ethylene phosphate (P(CL-EEP)), poly(ethylene-co-vinyl alcohol), poly(ethylenimine), polymethylmethacrylate (PMMA), hyaluronic acid, chitosan, pluronics, polyacrylamide, poly(vinyl alcohol) (PVA), polyhydroxyethylmethacrylate (polyHEMA), and combinations thereof. 
     
     
         16 . The method of  claim 11 , wherein the polymer is selected from the group consisting of 3-arm polyethylene glycol acrylate, 4-arm polyethylene glycol acrylate, 6-arm polyethylene glycol acrylate, 8-arm polyethylene glycol acrylate, and combinations thereof. 
     
     
         17 . The method of  claim 16 , wherein the polymer is 4-arm polyethylene glycol acrylate. 
     
     
         18 . The method of  claim 11 , wherein the buffer comprises water, HEPES, phosphate buffered saline, tris buffered saline, and combinations thereof. 
     
     
         19 . The method of  claim 11 , wherein the route of administration is selected from the group consisting of intraperitoneal, parenteral, subcutaneous, intra-articular, intravenous, intramuscular, and inhaled.