Hydrogels formed from polypeptide micelles and methods of use thereof
AssigneeDuke Univerity
InventorsGabriel P. Lopez, Ashutosh Chilkoti, Ali Ghoorchian, Joseph R. Simon
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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.
Claims20
A hydrogel comprised of reversibly crosslinked micelles, the hydrogel comprising:
- a. a plurality of a peptide polymer consisting essentially of a hydrophobic portion of 40 to 80 repeats of a VPGVG (SEQ ID NO:
- 1) peptide motif, a hydrophilic portion of 10 to 50 repeats of a VPGAGVPGGG (SEQ ID NO:
- 2) peptide motif, and a separate peptide metal binding sequence at 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.
A method of making a hydrogel comprised of reversibly crosslinked micelles, the method comprising:
- heating a plurality of a peptide polymer consisting essentially of a hydrophobic portion of 40 to 80 repeats of a VPGVG (SEQ ID NO:
- 1) peptide motif, a hydrophilic portion of 10 to 50 repeats of a VPGAGVPGGG (SEQ ID NO:
- 2) peptide motif, and a separate peptide metal binding sequence at 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.
A hydrogel loaded with a therapeutic molecule, the hydrogel comprising:
- a. a plurality of a peptide polymer consisting essentially of a hydrophilic portion of 60 to 100 repeats of a VPGAG (SEQ ID NO:
- 6) peptide motif and a separate peptide metal binding sequence at a terminus of the hydrophilic portion;
- and having 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;
- 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.
A method of making a hydrogel loaded with a therapeutic agent, the method comprising:
- attaching a hydrophobic therapeutic agent at a terminus of a plurality of a peptide polymer consisting essentially of 60 to 100 repeats of a VPGAG (SEQ ID NO:
- 6) peptide motif and a separate peptide metal binding sequence at an opposing terminus, wherein the peptide polymer takes the form of a plurality of micelles having the attached 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.
Dependencies are inferred from the claim text.