Biocompatible chemically crosslinked hydrogels for glucose sensing
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.
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.