PVA-boronic acid containing copolymer compositions for protein delivery

• US 9,345,773 B2
• Filed: 08/08/2011
• Issued: 05/24/2016
• Est. Priority Date: 06/23/2011
• Status: Expired due to Fees

• Current Assignee: Indian Institute of Technology Kharagpur
• Original Assignee: Indian Institute of Technology Kharagpur
• Inventors: Kumar, Ashok, Reddy, Rachamalla Maheedhar
• Primary Examiner(s): Ziska, Suzanne
• Assistant Examiner(s): WHEELER, THURMAN MICHAEL
• Application Number:
  US13/880,299
• Publication Number:
  US 20130209529A1
• Time in Patent Office: 1,751 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/78 of acrylic acid or derivatives thereof
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: C08F 220/34 Esters containing nitrogen , e.g. N,N-dimethylaminoethyl (meth)acrylate
• CPC Class Codes: C08F 220/54 Amides , e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
• CPC Class Codes: C08F 220/56 Acrylamide; Methacrylamide
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 33/24 Homopolymers or copolymers of amides or imides

Abstract

Provided herein are phenylboronate containing co-polymers (PCC), compositions containing PCC and polyvinyl alcohol (PVA), such compositions further including proteins, methods of making these compositions by water in oil polymerization, and methods of using the protein containing compositions for releasing proteins. Such phenylboronate containing co-polymers are of Formula I: where m, n, p, x, R¹-R⁵, L, X¹ and X² are defined in the application.

Claims

1. A particulate comprising a composition comprising polyvinyl alcohol and a co-polymer;

wherein the co-polymer is;

poly-((acrylamide)_m-co-(N-acryloyl-3-aminophenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

poly-((N-isopropylacrylamide)_m-co-(N-acryloyl-3-aminophenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

poly-((N-isopropylacrylamide)_m-co-(4-vinylphenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

poly-((acrylamide)_m-co-(4-vinylphenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

or

poly-((N,N-dimethylacrylamide)_m-co-(4-vinylphenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

wherein,

m is from 150000 to 220000;

n is from 4000 to 6000; and

p is from 3500 to 5500.

2. The particulate of claim 1, wherein the particulate is a sphere.

3. The particulate of claim 2, wherein the sphere has a diameter from 200 nm to 50 μ

m.

6. The particulate of claim 1 further comprising a protein, wherein the protein comprises a hormone, a growth factor, a cytokine, a soluble receptor, an enzyme, a monoclonal antibody, a peptide vaccine, or bovine serum albumin.

7. The particulate of claim 6, wherein the protein comprises insulin, vasopressin, calcitonin, growth hormone, luteinizing hormone releasing hormone, erythropoietin, insulin-like growth factor, epidermal growth factor, nerve growth factor, IL-1α

, interferon α

, interferon γ

, interleukin 2, tumor necrosis factor receptor, asparaginase, prolidase, lysozyme, streptokinase, urokinase, group B streptococcus antigen vaccine, tetanus toxoid, diphtheria toxoid, encephalitis virus vaccine, or bovine serum albumin (BSA).

8. The particulate of claim 7, wherein the protein is bovine serum albumin (BSA).

4. A method of preparing a particulate, the method comprising:

adding separately to an oil phase, a polyvinyl alcohol, a radical initiator, a compound of Formula II, a compound of Formula III, and a compound of Formula IV to form a mixture; and

polymerizing the mixture to form a particulate of;

poly-((acrylamide)_m-co-(N-acryloyl-3-aminophenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

poly-((N-isopropylacrylamide)_m-co-(N-acryloyl-3-aminophenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

poly-((N-isopropylacrylamide)_m-co-(4-vinylphenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

poly-((acrylamide)_m-co-(4-vinylphenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p;

or

poly-((N,N-dimethylacrylamide)_m-co-(4-vinylphenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

where m is from 150000 to 220000;

n is from 4000 to 6000; and

p is from 3500 to 5500;

wherein;

5. A method of releasing a protein from a particulate, the method comprising contacting the particulate with a monosaccharide to release the protein;

wherein the particulate comprises a composition comprising a protein, polyvinyl alcohol, and a co-polymer;

the co-polymer is;

poly-((acrylamide)_m-co-(N-acryloyl-3-aminophenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

poly-((N-isopropylacrylamide)_m-co-(N-acryloyl-3-aminophenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

poly-((N-isopropylacrylamide)_m-co-(4-vinylphenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

poly-((acrylamide)_m-co-(4-vinylphenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p;

or

poly-((N,N-dimethylacrylamide)_m-co-(4-vinylphenylboronic acid)_n-co-(N,N-dimethylaminoethylmethacrylate)_p);

wherein,

m is from 150000 to 220000;

n is from 4000 to 6000;

p is from 3500 to 5500; and

the protein comprises a hormone, a growth factor, a cytokine, a soluble receptor, an enzyme, a monoclonal antibody, a peptide vaccine, or bovine serum albumin.

9. The method of claim 5, wherein the protein comprises insulin, vasopressin, calcitonin, growth hormone, luteinizing hormone releasing hormone, erythropoietin, insulin-like growth factor, epidermal growth factor, nerve growth factor, IL-1α

, interferon α

, interferon γ

, interleukin 2, tumor necrosis factor receptor, asparaginase, prolidase, lysozyme, streptokinase, urokinase, group B streptococcus antigen vaccine, tetanus toxoid, diphtheria toxoid, encephalitis virus vaccine, or bovine serum albumin (BSA).

10. The method of claim 9 wherein the protein is bovine serum albumin (BSA).