US2019076373A1PendingUtilityA1

Injectable preformed macroscopic 3-dimensional scaffolds for minimally invasive administration

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Assignee: HARVARD COLLEGEPriority: Apr 28, 2011Filed: Jul 11, 2018Published: Mar 14, 2019
Est. expiryApr 28, 2031(~4.8 yrs left)· nominal 20-yr term from priority
Inventors:Sidi A. BencherifDavid J. MooneyDavid A. EdwardsRoger Warren Sands
A61L 2300/64A61L 2400/06A61L 27/52A61K 2039/55522A61L 2400/16A61L 27/50A61L 27/54A61K 9/7007A61P 37/02A61L 2300/258A61L 2300/252A61K 2039/55561A61L 27/20A61L 2430/34A61K 2039/64A61P 41/00A61L 27/56A61P 35/00A61K 39/0011C08L 5/04
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Claims

Abstract

The invention provides polymer compositions for cell and drug delivery.

Claims

exact text as granted — not AI-modified
1 - 28 . (canceled) 
     
     
         29 . An injectable cell-compatible highly crosslinked cryogel polymer composition comprising open interconnected pores,
 wherein the cryogel comprises at least 75% pores;   wherein the cryogel polymer composition is characterized by shape memory following deformation by compression or dehydration; and   wherein the cryogel composition comprises a crosslinked gelatin polymer or a crosslinked alginate polymer.   
     
     
         30 . The cryogel polymer composition of  claim 29 , wherein the cryogel composition is characterized by shape memory following deformation by compression through a needle. 
     
     
         31 . The cryogel polymer composition of  claim 29 , further comprising a biomolecule. 
     
     
         32 . The cryogel polymer composition of  claim 31 , wherein the biomolecule comprises a small molecule, a nucleic acid, or a protein. 
     
     
         33 . The cryogel polymer composition of  claim 32 , wherein the biomolecule is a protein that recruits a cell into the cryogel composition upon injection into a subject. 
     
     
         34 . The cryogel polymer composition of  claim 33 , wherein the protein is GM-CSF. 
     
     
         35 . The cryogel polymer composition of  claim 33 , wherein the cell is an immune cell. 
     
     
         36 . The cryogel polymer composition of  claim 35 , wherein the immune cell is a dendritic cell. 
     
     
         37 . The cryogel polymer composition of  claim 29 , further comprising an adjuvant. 
     
     
         38 . The cryogel polymer composition of  claim 37 , wherein the adjuvant is cytosine-guanosine oligonucleotide (CpG-ODN). 
     
     
         39 . The cryogel polymer composition of  claim 29 , wherein the gelatin or alginate is acrylated or methacrylated. 
     
     
         40 . The cryogel polymer composition of  claim 39 , wherein the alginate is a methacrylated alginate macromonomer with a concentration of about 1% (w/v). 
     
     
         41 . The cryogel polymer composition of  claim 29 , wherein the cryogel composition is characterized by at least 50% polymer crosslinking. 
     
     
         42 . The cryogel polymer composition of  claim 41 , wherein the cryogel composition is characterized by 50-98% polymer crosslinking. 
     
     
         43 . The cryogel polymer composition of  claim 29 , wherein the cryogel comprises:
 (a) at least 90% water in a hydrated state; or   (b) less than 25% water in a compressed state.   
     
     
         44 . The cryogel polymer composition of  claim 29 , further comprising an antigen. 
     
     
         45 . The cryogel polymer composition of  claim 44 , wherein the antigen comprises a cancer antigen. 
     
     
         46 . The cryogel polymer composition of  claim 45 , wherein the cancer antigen comprises a protein, a peptide, or a living attenuated cancer cell. 
     
     
         47 . The cryogel polymer composition of  claim 45 , wherein the cancer antigen comprises a melanoma antigen, or an attenuated melanoma cell. 
     
     
         48 . The cryogel polymer composition of  claim 47 , wherein the attenuated melanoma cell comprises an irradiated melanoma cell. 
     
     
         49 . The cryogel polymer composition of  claim 29 , comprising a eukaryotic cell in one or more of the open interconnected pores. 
     
     
         50 . The cryogel polymer composition of  claim 49 , wherein the eukaryotic cell comprises a live attenuated cancer cell. 
     
     
         51 . The cryogel polymer composition of  claim 29 , wherein the cryogel composition is between 100 μm 3  to 100 mm 3  in size. 
     
     
         52 . The cryogel polymer composition of  claim 29 , further comprising a microsphere. 
     
     
         53 . The cryogel polymer composition of  claim 52 , wherein the microsphere comprises PLGA. 
     
     
         54 . The cryogel polymer composition of  claim 52 , wherein the microsphere comprises GM-CSF. 
     
     
         55 . The cryogel polymer composition of  claim 52 , wherein the microsphere comprises a drug. 
     
     
         56 . The cryogel polymer composition of  claim 29 , comprising GM-CSF, a pathogen-associated molecular pattern (PAMP), and a tumor antigen. 
     
     
         57 . The cryogel polymer composition of  claim 29 , further comprising a magnetic particle. 
     
     
         58 . The cryogel polymer composition of  claim 57 , wherein the magnetic particle comprises a Fe 3 O 4  nanoparticle or a Fe 3 O 4  micro-particle. 
     
     
         59 . The cryogel polymer composition of  claim 29 , further comprising a mechanophore molecule. 
     
     
         60 . The cryogel polymer composition of  claim 59 , wherein the mechanophore molecule comprises a polydiacetylene liposome. 
     
     
         61 . The cryogel polymer composition of  claim 29 , wherein the cryogel composition comprises macropores having a diameter of 10 μm to 600 μm. 
     
     
         62 . The cryogel polymer composition of  claim 29 , further comprising a polymer selected from the group consisting of heparin, dextran, carob gum, PEG, a PEG derivative, collagen, chitosan, carboxymethylcellulose, pullulan, PVA, PHEMA, PNIPAAm, and PAAc. 
     
     
         63 . The cryogel polymer composition of  claim 29 , wherein the composition is in the shape of a disc, a cylinder, a square, a rectangle, or a string. 
     
     
         64 . The cryogel polymer composition of  claim 29 , wherein the composition has a Young's modulus of 4±2 kPa. 
     
     
         65 . A method of minimally invasive administration of a polymer scaffold for agent delivery to a subject, comprising:
 administering a cryogel polymer composition of  claim 29  to the subject.   
     
     
         66 . The method of  claim 65 , wherein the administration of the cryogel polymer composition is through injecting. 
     
     
         67 . The method of  claim 65 , wherein the method elicits an immune response the subject. 
     
     
         68 . The method of  claim 67 , wherein the cryogel composition comprises a biomolecule that recruits an immune cell to the cryogel composition. 
     
     
         69 . The method of  claim 67 , wherein the cryogel composition further comprises an adjuvant. 
     
     
         70 . The method of  claim 67 , wherein the cryogel composition further comprises an antigen. 
     
     
         71 . The method of  claim 70 , wherein the antigen comprises a cancer antigen. 
     
     
         72 . The method of  claim 71 , wherein the immune response is an anti-cancer immune response. 
     
     
         73 . The method of  claim 71 , wherein the cancer antigen comprises a live attenuated cancer cell. 
     
     
         74 . The method of  claim 73 , wherein cell viability is 90% or more following passage of the cryogel composition through a needle or other delivery apparatus. 
     
     
         75 . A syringe comprising:
 (i) a needle;   (ii) a reservoir comprising the cryogel composition of  claim 29 ; and   (iii) a plunger.   
     
     
         76 . The syringe of  claim 75 , comprising a 16-gauge, an 18-gauge, a 22-gauge, a 24-gauge, a 26-gauge, a 28-gauge, a 30-gauge, a 32-gauge, or a 34-gauge needle. 
     
     
         77 . The syringe of  claim 75 , comprising an 18 to 30-gauge needle. 
     
     
         78 . The syringe of  claim 75 , wherein the cryogel composition further comprises cells, wherein 90% or more of the cells survive passage of the cryogel composition through a needle. 
     
     
         79 . The syringe of  claim 78 , wherein the cells comprise live attenuated cancer cells.

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