Polymeric system for drug delivery and solute separation

• US 6,565,872 B2
• Filed: 02/16/2000
• Issued: 05/20/2003
• Est. Priority Date: 02/16/1999
• Status: Expired due to Term

• Current Assignee: Xiao Y.U. Wu
• Original Assignee: Xiao Y.U. Wu
• Inventors: Wu, Xiao Yu, Yam, Frank
• Primary Examiner(s): Spear, James M.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/504,884
• Publication Number:
  US 20020001571A1
• Time in Patent Office: 1,189 Days
• Field of Search: 424/484, 424/426, 424/486, 424/488, 424/489, 424/427, 424/428, 424/464, 514/912, 514/913, 514/914, 514/915
• US Class Current: 424/426
• CPC Class Codes: A61K 9/009 Sachets, pouches characterised by the material or function of the envelope with gastric retention A61K9/0065; sachets which are not administered but function merely as a container are classified according to the content, e.g. sachets comprising powder for reconstitution of a drink A61K9/0095
• 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 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: B01D 69/02 characterised by their properties
• CPC Class Codes: B01D 69/14111 with nanoscale dispersed material, e.g. nanoparticles
• CPC Class Codes: B01D 71/22 Cellulose ethers
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Described is a composite polymeric system to provide enhanced stimuli-responsiveness. The first aspect provides particles where the particles are made of stimuli-responsive polymer which responds to various stimuli such as temperature and pH change. Incorporated with this particle is a second polymer which in turn is relatively insensitive to stimuli. The invention can be potentially applied to other systems comprising a swellable hydrogel and a nonswellable hydrophobic polymer.

Claims

1. A composition for a composite polymer system comprising particles of a stimuli-responsive polymer dispersed within a matrix, said matrix comprising at least one second polymer, wherein said at least one second polymer is non-swellable, hydrophobic and membrane-formable.

2. A composition according to claim 1 wherein the stimuli-responsive polymer is selected from the group consisting of polymers of R-acrylamide, R1-acrylate and R2-acrylic acid;

and polyethylene glycol, where R, R1, and R2 may each be H or alkyl.

3. A composition according to claim 2 wherein said second polymer is selected from the group consisting of polysaccharides;

cellulose;

polyesters;

polyanhydrides;

poly(othoesters); and

polyurethane.

4. A composition according to claim 3 wherein the composition is biocompatable and biodegradable.

5. The composition according to claim 1 comprising poly(N-isopropylacrylamide-co-methacrylic acid) and ethylcelulose.

6. A composite polymer system according to claim 1 wherein the stimuli-responsive polymer is swellable.

7. A composition according to claim 1 wherein said second polymer is also, membrane forming.

8. A composition according to claim 7 wherein the second polymer also forms a continuous phase with said stimuli-responsive polymer.

9. A composition according to claim 1 wherein said second polymer is selected from the group consisting of cellulose, ethylcellulose, methylcellulose, propylcellulose, methoxypropylcellulose, cellulose nitrate, poly(vinyl alcohol), poly(vinyl chloride), polystyrene, polyethylene, polypropylene, poly(ethylene-co-vinyl acetate), poly(hydroxybutyric acid), poly(hydroxyvalerianic acid-co-hydroxybutyric acid), poly(lactic acid), poly(glycolic acid), poly(lactic acid-co-glycolic acid), poly(epsilon (-caprolactones), poly(epsilon(-caprolactone-co-DL-lactic acid), poly(maleic anhydride), polyamides, gelatin, chitosan, collagen, poly(hydroxyalkyl)-L-glutamines, poly(gamma(-ethyl-L-glutaminate-co-glutamic acid), poly(L-leucine-co-L-aspartic acid), poly(proline-co-glutamic acid), poly(alkyl 2-cyanoacrylates), polyurethanes, poly(methyl methacrylate), poly(methyl methacrylate-co-methacrylic acid) and poly(methacrylate-co-hydroxypropyl methacrylate).

10. The composition according to claim 1, wherein the stimuli-responsive polymer particles form channels in the matrix in response to changes in external stimuli.

11. A method of preparing a composite polymer system according to claim 1 comprising:

(a) preparing particles with a stimuli-responsive polymer;

(b) adding and mixing at least one second polymer under conditions which permit dispersion of the particles in the second polymer; and

(c) casting the resulting composite polymer system, wherein said at least one second polymer is non-swellable and hydrophobic.

12. A method according to claim 11 wherein the step of mixing is carried out by a method selected from the group consisting of melting the polymers and mixing the polymers in solution.

13. A method according to claim 11 wherein the stimuli-responsive polymer is swellable.

14. A method of solute separation and filtration comprising the following steps:

(i) preparing a composite polymer system according to the method of claim 11;

(ii) incorporating a substance within the system; and

(iii) applying the system under conditions which result in solute separation and filtration.

15. A method of temperature, pH and ionic strength, biochemical or ion-responsive drug delivery comprising the following steps:

(i) preparing a composite polymer system according to the method of claim 11;

(ii) incorporating a substance within the system; and

(iii) applying the system under conditions which result in temperature, pH and ionic strength, biochemical or ion-responsive drug delivery.

16. A method for diagnosis and monitoring comprising the following steps:

(i) preparing a composite polymer system according to the method of claim 11;

(ii) incorporating a substance within the system; and

(iii) applying the system under conditions which result in diagnosis and monitoring.

17. A method of protein and peptide drug delivery comprising the following steps:

(i) preparing a composite polymer system according to the method of claim 11;

(ii) incorporating a substance within the system; and

(iii) applying the system under conditions which result in protein or peptide drug delivery.

18. A method of coating and microencapsulation of solid dosage forms or live cells comprising the following steps:

(i) preparing a composite polymer system according to the method of claim 11;

(ii) incorporating a substance within the system; and

(iii) applying the system under conditions which result in coating and microencapsulation of solid dosage forms or live cells.

19. A method according to claim 11 wherein said second polymer is also, membrane forming.

20. A method according to claim 19 wherein the second polymer also forms a continuous phase with said stimuli-responsive polymer.

21. A method according to claim 11 wherein the stimuli-responsive polymer is selected from the group consisting of polymers of R-acrylamide, R1-acrylate and R2-acrylic acid;

and polyethylene glycol, where R, R1, and R2 may each be H or alkyl.

22. A method according to claim 21 wherein said second polymer is selected from the group consisting of polysaccharides;

cellulose;

polyesters;

polyanhydrides;

poly(othoesters); and

polyurethane.

23. A method according to claim 21, wherein said second polymer is selected from the group consisting of cellulose, ethylcellulose, methylcellulose, propylcellulose, methoxypropylcellulose, cellulose nitrate, poly(vinyl alcohol), poly(vinyl chloride), polystyrene, polyethylene, polypropylene, poly(ethylene-co-vinyl acetate), poly(hydroxybutyric acid), poly(hydroxyvalerianic acid-co-hydroxybutyric acid), poly(lactic acid), poly(glycolic acid), poly(lactic acid-co-glycolic acid), poly(epsilon(-caprolactones), poly(epsilon(-caprolactone-co-DL-lactic acid), poly(maleic anhydride), polyamides, gelatin, chitosan, collagen, poly(hydroxyalkyl)-L-glutamines, poly(gamma(-ethyl-L-glutaminate-co-glutamic acid), poly(L-leucine-co-L-aspartic acid), poly(proline-co-glutamic acid), poly(alkyl 2-cyanoacrylates), polyurethanes, poly(methyl methacrylate), poly(methyl methacrylate-co-methacrylic acid) and poly(methacrylate-co-hydroxypropyl methacrylate).