Back to results
US 11,298,424 B2Granted
Non-ionic and thermoresponsive diblock copolypeptide hydrogels for delivery of molecules and cells
AssigneeThe Regents of the University of California
InventorsTimothy J. Deming, Michael V. Sofroniew, Shanshan Zhang
Life of this patent
Estimating the term…
Abstract
The present invention is directed to copolypeptide hydrogels (DCH) containing non-ionic hydrophilic residues (DCHEO), incorporation of thermoresponsive elements into DCHEO, to generate thermoresponsive DCH (DCHT), and hydrogels that include a combination of DCHEO and DCHT. The invention includes preparation, uses, compositions containing the hydrogels and methods of tuning the hydrogels. The hydrogels can be used to deliver an agent or cells to an organism.
Claims15
A composition comprising:
- an aqueous medium;
- and
- a copolypeptide hydrogel forming composition,
- wherein said copolypeptide composition comprises at least one hydrophilic polypeptide segment or hydrophilic copolypeptide segment and at least one hydrophobic polypeptide segment or hydrophobic copolypeptide segment,
- wherein the hydrophilic polypeptide segment or hydrophilic copolypeptide segment consists of residues selected from lysine, glutamate, aspartate, arginine, ornithine, homoarginine, a residue of Formula I, a residue of Formula II, a residue of Formula III, a residue of Formula IV, a residue of Formula V, a residue of Formula VI, and combinations thereof;
- and
- wherein the hydrophilic polypeptide segment or hydrophilic copolypeptide segment contains less than 50 mol % ionic amino acid residues, wherein an ionic amino acid residue is an amino acid residue having a charged side-chain at pH=7 in water;
- wherein:
- R1 is, independently at each occurrence, —(CH2CH2O)nCH3 or
- R1a is —(CH2CH2O)nCH3;
- R2 is, independently at each occurrence, —(CH2CH2O)nCH3 or
- R2a is —(CH2CH2O)nCH3;
- X1 is O;
- Y1 is, independently at each occurrence, absent or O;
- R3 is, independently at each occurrence, selected from —(CH2CH2O)mCH3, —CH2CH2CH2(sugar), and -sugar;
- X2 is, independently at each occurrence, absent or O;
- Y2 is, independently at each occurrence, absent or O;
- R4 is, independently at each occurrence, selected from —(CH2CH2O)nCH3, —CH2CH2CH2(sugar), —CH2CHR4aC(O)OR4b, and —CH2CH2SO2CH2CH2SR4c;
- R4a is, independently at each occurrence, —H or —CH3;
- R4b is —(CH2CH2O)CH3;
- R4c is —(CH2CH2O)nCH3;
- X3 is, independently at each occurrence, absent or O;
- Y3 is, independently at each occurrence, absent or O;
- R5 is, independently at each occurrence, —(CH2CH2O)nCH3 or -sugar;
- n is an integer from 1-4;
- m is an integer from 1-6;
- and
- p is an integer from 1-9.
25 more elements
A method of delivering an agent or a cell into an organism comprising:
- a) creating a mixture comprising:
- the agent or the cell,
- an aqueous medium, and
- a copolypeptide hydrogel forming composition, wherein said copolypeptide composition comprises at least one hydrophilic polypeptide segment or hydrophilic copolypeptide segment and at least one hydrophobic polypeptide segment or hydrophobic copolypeptide segment;
- wherein the hydrophilic polypeptide segment or hydrophilic copolypeptide segment consists of residues selected from lysine, glutamate, aspartate, arginine, ornithine, homoarginine, a residue of Formula I, a residue of Formula II, a residue of Formula III, a residue of Formula IV, a residue of Formula V, a residue of Formula VI, and combinations thereof;
- and wherein the hydrophilic polypeptide segment or hydrophilic copolypeptide segment contains less than 50 mol % ionic amino acid residues, wherein an ionic amino acid residue is an amino acid residue having a charged side-chain at pH=7 in water;
- and
- b) introducing the mixture into the organism;
- wherein:
- R1 is, independently at each occurrence, —(CH2CH2O)nCH3 or
- R1a is —(CH2CH2O)nCH3;
- R2 is, independently at each occurrence, —(CH2CH2O)nCH3 or
- R2a is —(CH2CH2O)nCH3;
- X1 is O;
- Y1 is, independently at each occurrence, absent or O;
- R3 is, independently at each occurrence, selected from —(CH2CH2O)mCH3, —CH2CH2CH2(sugar), and -sugar;
- X2 is, independently at each occurrence, absent or O;
- Y2 is, independently at each occurrence, absent or O;
- R4 is, independently at each occurrence, selected from —(CH2CH2O)pCH3, —CH2CH2CH2(sugar), —CH2CHR4aC(O)OR4b, and —CH2CH2SO2CH2CH2SR4c;
- R4a is, independently at each occurrence, —H or —CH3;
- R4b is —(CH2CH2O)pCH3;
- R4c is —(CH2CH2O)pCH3:
- X3 is, independently at each occurrence, absent or O;
- Y3 is, independently at each occurrence, absent or O;
- R5 is, independently at each occurrence, —(CH2CH2O)nCH3 or -sugar;
- n is an integer from 1-4;
- m is an integer from 1-6;
- and
- p is an integer from 1-9.
26 more elements
Dependencies are inferred from the claim text.