Biocompatible chemically crosslinked hydrogels for glucose sensing

• US 7,432,069 B2
• Filed: 12/05/2005
• Issued: 10/07/2008
• Est. Priority Date: 12/05/2005
• Status: Expired due to Fees

• Current Assignee: Echo Therapeutics Incorporated
• Original Assignee: Sontra Medical Corporation (Echo Therapeutics Incorporated)
• Inventors: Warner, Nicholas F., Schramm, Helice A., Barman, Shikha P.
• Primary Examiner(s): GITOMER, RALPH J
• Application Number:
  US11/275,043
• Publication Number:
  US 20070128681A1
• Time in Patent Office: 1,037 Days
• Field of Search: 435/14, 514/866, 523/105, 528/392, 600/347, 604/304
• US Class Current: 435/14
• CPC Class Codes: B01J 13/0091 Preparation of aerogels, e.g. xerogels

Abstract

An hydrogel incorporating a biologically active component is provided that is useful as an interface material for transdermal sensing applications. Specifically, the hydrogel has a crosslinked gel structure and a biologically active component incorporated into the crosslinked gel structure, the biologically active component being capable of converting glucose into a compound having potentiometric activity.

Claims

1. A transdermal biosensor including a skin-contacting hydrogel comprising an electrode, a crosslinked gel structure, and a biologically active enzyme incorporated into the crosslinked gel structure, the biologically active enzyme which converts glucose into a compound having potentiometric activity that is detectable when the biosensor is placed on a patient'"'"'s skin, wherein the hydrogel is obtained from a solution comprising:

a macromer comprising at least one hydrophilic polymeric block including polyethylene glycol that is end-terminated with at least one cross-linkable group;

an initiator; and

the biologically active enzyme, wherein the macromer solution comprises greater than 10% macromer (w/v) and the macromer is of sufficient molecular weight to form a network mesh upon crosslinking that entraps the biologically active enzyme.

2. The hydrogel biosensor according to claim 1, wherein the macromer is obtained from dry macromer having an inhibitor content within the range of about 10 to 500 ppm.

3. The hydrogel biosensor according to claim 1, wherein the macromer is a tri-, tetra-, penta-, star, dendritic or branched macromer.

4. The hydrogel biosensor according to claim 1, further comprising a second macromer having a different structure than the first macromer.

5. The hydrogel biosensor according to claim 1, wherein the macromer is a copolymer further comprising a vinyl moiety.

6. The hydrogel biosensor according to claim 1, wherein the vinyl moiety is n-vinyl acetate or n-vinyl acrylate.

7. The hydrogel biosensor according to claim 1, wherein the macromer solution further comprises a non.-crosslinkable polymer.

8. The A hydrogel biosensor according to claim 7, wherein the non-crosslinkable polymer is polyacrylic acid.

9. The A hydrogel biosensor according to claim 1, wherein the cross-linkable group is an ethylenically unsaturated group.

10. The hydrogel biosensor according to claim 9, wherein the ethylenically unsaturated group is an acrylate, a diacrylate, a methacrylate, an isocyanate, a di-isocyanate, an epoxide, an isothiocyanate, an aldehyde, an amine, a sulfonic acid or a carboxylic acid.

11. The hydrogel biosensor according to claim 1, wherein the macromer solution further comprises an excipient that is different than the macromer.

12. The hydrogel biosensor according to claim 11, wherein the excipient is sodium lauryl sulfate, n-vinyl acetate, acetic acid, sodium chloride, phosphates, trehalose, polyacrylic acid, chitosan, a hyaluronic acid, a PEG, a mPEG-monoacrylate, polyethyleneimine, a dendritic polyethyleneimine (PEL), a poly(amidoamine) (PAMAM), carboxymethycellulose (CMC), poly(vinyl pyrrolidone)(PVP), poly(vinyl acetate) (PVAc), poly(2-acrylamide-2-methyl-1-propane-sulfonic acid) (PMP), a sorbitan, a Tween, a Span, or a derivatized PEGs.

13. The hydrogel biosensor according to claim 1, wherein a initiator concentration in the macromer solution is 2500 ppm or less.

14. The hydrogel biosensor according to claim 1, wherein degree of end-capping of the macromer exceeds about 90%

15. The A hydrogel biosensor according to claim 1, wherein the enzyme is glucose oxidase.

16. The A hydrogel biosensor according to claim 1, wherein at least 60% of the bioactivity of the incorporated biologically active molecule is maintained when measured by potentiometry over seventeen consecutive additions of glucose at a concentration of 2.5 mg/dL with eight minutes elapsing between each consecutive addition of glucose.

17. The hydrogel biosensor according to claim 1, wherein the hydrogel retains moisture such that it maintains at least 60% of its fully hydrated weight after contact with skin for a period of 24 hours.

18. The hydrogel biosensor according to claim 1, wherein the hydrogel swells at least about 15% after soaking in phosphate buffered saline for 15 minutes and swells less than about 30% after soaking in phosphate buffered saline for 12 hours.

19. The hydrogel biosensor according to claim 1,wherein the crosslinked get structure is obtained from a macromer having an average molecular weight within a range of 3 to 4 K Daltons.

20. The hydrogel biosensor according to claim 19, wherein the macromer is a polyethylene glycol multifunctional acrylate.

21. The hydrogel biosensor according to claim 1, wherein the macromer solution comprises at least 15% w/v macromer.