HYDROGELS FORMED FROM POLYPEPTIDE MICELLES AND METHODS OF USE THEREOF
First Claim
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1. A hydrogel comprised of reversibly crosslinked micelles, the hydrogel comprising:
- a. a plurality of a peptide polymer having a hydrophobic portion, a hydrophilic portion, and a peptide metal binding sequence near a terminus of the hydrophilic portion, wherein the peptide polymer is in the form of a plurality of micelles having the hydrophobic portion at a core of the micelles and the metal binding sequence at a surface of the micelles; and
b. a plurality of metal ions bound at the metal binding sequences, wherein the plurality of micelles are reversibly crosslinked through the bound metal ions.
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Abstract
The presently disclosed subject matter is directed to compositions, methods, and systems (e.g., platforms) comprising the same, the systems comprising, consisting of, or consisting essentially of micro- and macro-hydrogels that are formed from polypeptide micelles. The systems have enhanced mechanical properties that can be useful in a wide variety of applications, can be used for controlled release of drug-loaded micelles, and can be designed to reversibly assemble and disassemble on demand.
12 Citations
25 Claims
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1. A hydrogel comprised of reversibly crosslinked micelles, the hydrogel comprising:
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a. a plurality of a peptide polymer having a hydrophobic portion, a hydrophilic portion, and a peptide metal binding sequence near a terminus of the hydrophilic portion, wherein the peptide polymer is in the form of a plurality of micelles having the hydrophobic portion at a core of the micelles and the metal binding sequence at a surface of the micelles; and b. a plurality of metal ions bound at the metal binding sequences, wherein the plurality of micelles are reversibly crosslinked through the bound metal ions.
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2. The hydrogel of claim 1, wherein the peptide polymer comprises an elastin-like polypeptide (ELP).
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3. The hydrogel of claim 1, wherein the hydrophobic portion of the peptide polymer comprises 40 to 80 repeats of a VPGVG (SEQ ID NO:
- 1) peptide motif.
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4. The hydrogel of claim 1, wherein the hydrophilic portion of the peptide polymer comprises 10 to 50 repeats of a VPGAGVPGGG (SEQ ID NO:
- 2) peptide motif.
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5. The hydrogel of claim 1, wherein the peptide metal binding sequence comprises a motif HEDGHWDGSEHGY (SEQ ID NO:
- 3) and the metal comprises one or more of transition metals Zn2+, Ni2+, or Cu2+.
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6. The hydrogel of claim 5, wherein the metal is Zn2+.
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7. The hydrogel of claim 1, wherein the peptide polymer further comprises a hydrophobic therapeutic agent attached to the hydrophobic portion at the core of the micelles.
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8. The hydrogel of claim 7, wherein the hydrophobic therapeutic agent is attached to the hydrophobic portion through a linker, and wherein the linker includes an enzymatic cleavage site to allow for release of the hydrophobic therapeutic agent from the micelle.
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9. The hydrogel of claim 7, wherein the hydrophobic therapeutic agent is attached to the hydrophilic portion through a linker, and wherein the linker includes a pH sensitive cleavage site to allow for release of the hydrophobic therapeutic agent from the micelle.
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10. The hydrogel of claim 1, further comprising an interpenetrating mesh consisting essentially of covalently crosslinked polymers, wherein the mesh surrounds the reversibly crosslinked micelles without being covalently attached to the micelles.
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11. The hydrogel of claim 10, wherein the covalently crosslinked polymers comprise polypeptides, elastin-like polypeptides (ELP), biopolymers, synthetic polymers, or branched polymers, and combinations thereof.
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12. A method of making a hydrogel comprised of reversibly crosslinked micelles, the method comprising:
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heating a plurality of a peptide polymer having a hydrophobic portion, a hydrophilic portion, and a peptide metal binding sequence near a terminus of the hydrophilic portion, wherein the peptide polymer takes the form of a plurality of micelles having the hydrophobic portion at a core of the micelles and the metal binding sequences at a surface of the micelles; and adding a plurality of metal ions to the micelles, wherein the plurality of micelles are reversibly crosslinked through the bound metal ions at the metal binding sequences.
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13. The method of claim 12, wherein the peptide polymer further comprises a hydrophobic therapeutic agent attached to the hydrophobic portion, wherein the hydrophobic therapeutic agent is at the core of the micelles along with the hydrophobic portion.
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14. The method of claim 12, further comprising adding a plurality of a polymer and a crosslinking agent, wherein the plurality of polymers are covalently crosslinked to each other to form an interpenetrating mesh consisting essentially of the covalently crosslinked polymers, wherein the interpenetrating mesh surrounds the reversibly crosslinked micelles without being covalently attached to the micelles.
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15. A hydrogel loaded with a therapeutic molecule, the hydrogel comprising:
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a. a plurality of a peptide polymer having a hydrophilic portion and a peptide metal binding sequence at a terminus of the hydrophilic portion; and
a hydrophobic therapeutic agent attached near an opposing terminus of the hydrophilic portion, wherein the peptide polymer is in the form of a plurality of micelles having the hydrophobic therapeutic agent at a core of the micelles and the metal binding sequences at a surface of the micelles; andb. a plurality of metal ions bound at the metal binding sequences, wherein the plurality of micelles are reversibly crosslinked through the bound metal ions.
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16. The hydrogel of claim 15, wherein the peptide polymer comprises an elastin-like polypeptide (ELP).
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17. The hydrogel of claim 15, wherein the hydrophilic portion of the peptide polymer comprises from 60 to 100 repeats of a VPGAG (SEQ ID NO:
- 6) peptide motif.
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18. The hydrogel of claim 15, wherein the peptide metal binding site comprises a motif HEDGHWDGSEHGY (SEQ ID NO:
- 3) and the metal comprises one or more of transition metals Zn2+, Ni2+, or Cu2+.
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19. The hydrogel of claim 18, wherein the metal is Zn2+.
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20. The hydrogel of claim 15, wherein the hydrophobic therapeutic agent is attached to the hydrophilic portion through a linker, and wherein the linker includes an enzymatic cleavage site to allow for release of the hydrophobic therapeutic agent from the micelle.
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21. The hydrogel of claim 15, wherein the hydrophobic therapeutic agent is attached to the hydrophilic portion through a linker, and wherein the linker includes a pH sensitive cleavage site to allow for release of the hydrophobic therapeutic agent from the micelle.
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22. The hydrogel of claim 15, further comprising an interpenetrating mesh consisting essentially of covalently crosslinked polymers, wherein the mesh surrounds the reversibly crosslinked micelles without being covalently attached to the micelles.
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23. The hydrogel of claim 22, wherein the covalently crosslinked polymers comprise polypeptides, elastin-like polypeptides (ELP), biopolymers, synthetic polymers, or branched polymers, and combinations thereof.
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24. A method of making a hydrogel loaded with a therapeutic agent, the method comprising:
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attaching a hydrophobic therapeutic agent near a terminus of a hydrophilic portion of a plurality of a peptide polymer having a peptide metal binding sequence at an opposing terminus of the hydrophilic portion, wherein the peptide polymer takes the form of a plurality of micelles having the hydrophobic therapeutic agent a core of the micelles and the metal binding sequences at a surface of the micelles; and adding a plurality of metal ions to the micelles, wherein the plurality of micelles are reversibly crosslinked through the bound metal ions at the metal binding sequences.
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25. The method of claim 24, further comprising adding a plurality of a polymer and a crosslinking agent, wherein the plurality of polymers are covalently crosslinked to each other to form an interpenetrating mesh consisting essentially of the covalently crosslinked polymers, wherein the interpenetrating mesh surrounds the reversibly crosslinked micelles without being covalently attached to the micelles.
Specification