Implantation of encapsulated biological materials for treating diseases

Abstract

Methods of applying biocompatible coating materials around biological materials using photopolymerization while maintaining the pre-encapsulation status of the biological materials are disclosed. The coatings can be placed directly onto the surface of the biological materials or onto the surface of other coating materials that hold the biological materials. The components of the polymerization reactions that produce the coatings can include natural and synthetic polymers, macromers, accelerants, cocatalysts, photoinitiators, and radiation. Methods of utilizing these encapsulated biological materials to treat different human and animal diseases or disorders by implanting them into several areas in the body including the subcutaneous site are also disclosed. The coating materials can be manipulated to provide different degrees of biocompatibility, protein diffusivity characteristics, strength, and biodegradability to optimize the delivery of biological materials from the encapsulated implant to the host recipient while protecting the encapsulated biological materials from destruction by the host inflammatory and immune protective mechanisms without requiring long-term anti-inflammatory or anti-immune treatment of the host.

1 . A method of treating a disease or disorder comprising implanting a composition comprising:
 encapsulating devices comprising a conformal coating, and cell aggregates,   
     into an implantation site in an animal in need of treatment for said disease or disorder, wherein said composition has a cell density of at least about 100,000 cells/ml, wherein the conformal coating for the encapsulating devices comprises a polymerizable high density ethylenically unsaturated PEG having a molecular weight between 900 and 3,000 Daltons, and a sulfonated comonomer, and wherein the coating conforms to the size and shape of the cell aggregates. 
   
   
       2 . The method of  claim 1 , where the disease or disorder is selected from the group consisting of neurologic, cardiovascular, hepatic, endocrine, skin, hematopoietic, immune, neurosecretory, metabolic, systemic, and genetic. 
   
   
       3 . The method of  claim 1 , where the animal is a human. 
   
   
       4 . The method of  claim 1 , where the implanting is an injection. 
   
   
       5 . The method of  claim 1 , where the implantation site is selected from the group consisting of subcutaneous, intramuscular, intraorgan, arterial/venous vascularity of an organ, cerebro-spinal fluid, and lymphatic fluid. 
   
   
       6 . The method of  claim 5 , wherein the implantation site is subcutaneous and wherein the cell aggregates comprise islets. 
   
   
       7 . The method of  claim 1 , further comprising administering an immunosuppressant or anti-inflammatory agent. 
   
   
       8 . A method of treating a disease or disorder comprising implanting a therapeutically effective composition comprising a plurality of encapsulating devices having an average diameter of less than 400 μm, said encapsulating devices comprising encapsulated cell aggregates conformally coated in an encapsulation material, into an implantation site in an animal in need of treatment for said disease or disorder, wherein the composition comprises at least about 500,000 cells/ml and wherein the encapsulation material comprises a polymerizable high density ethylenically unsaturated PEG having a molecular weight between 900 and 3,000 Daltons, and a sulfonated comonomer, wherein the coating conforms to the size and shape of the cell aggregates. 
   
   
       9 . A method of encapsulating a biological material comprising:
 (a) adding a solution comprising a first buffer to the biological material;   (b) centrifuging the biological material to form a pelleted biological material;   (c) removing supernatant;   (d) adding a solution comprising a photoinitiator dye conjugated to a cell adsorbing material to the pelleted biological material;   (e) resuspending and incubating the pelleted biological material with the solution comprising the photoinitiator dye conjugated to the cell adsorbing material for an effective amount of time;   (f) centrifugating mixture;   (g) removing the solution comprising the photoinitiator dye conjugated to the cell adsorbing material;   (h) resuspending the pelleted biological material with a second solution comprising a second buffer;   (i) centrifugating and removing the second buffer;   (j) resuspending and mixing the biological material with a photoactive polymer solution comprising a polymerizable high density ethylenically unsaturated PEG and a sulfonated comonomer; and   (k) irradiating the resuspended biological material with a photoactive polymer solution with an energy source to form an encapsulated biological material.   
   
   
       10 . The method of  claim 9 , where the cell adsorbing material is a polycationic polymer. 
   
   
       11 . The method of  claim 10 , where the polycationic polymer is a PAMAM Dendrimer or poly(ethyleneimine). 
   
   
       12 . The method of  claim 9 , wherein the biological material is an organ, tissue or cell. 
   
   
       13 . The method of  claim 9 , wherein the biological material is a cluster of insulin producing cells. 
   
   
       14 . The method of  claim 9 , wherein the photoinitiator is selected from the group consisting of carboxyeosin, ethyl eosin, eosin Y, fluorescein, 2,2-dimethoxy, 2-phenylacetophenone, 2-methoxy, 2-phenylacetophenono, camphorquinone, rose bengal, methylene blue, erythrosin, phloxine, thionine, riboflavin and methylene green. 
   
   
       15 . The method of  claim 9 , where the sulfonated comonomer is selected from the group consisting of 2-acrylamido-2-methyl-1-propanesulfonic acid, vinylsulfonic acid, 4-styrenesulfonic acid, 3-sulfopropyl acrylate, 3-sulfopropyl methacrylate, and n-vinyl maleimide sulfonate. 
   
   
       16 . The method of  claim 9 , further comprising a cocatalyst selected from the group consisting of triethanolamine, triethylamine, ethanolamine, N-methyl diethanolamine, N,N-dimethyl benzylamine, dibenzyl amino, N-benzyl ethanolamine, N-isopropyl benzylamine, tetramethyl ethylenediamine, potassium persulfate, tetramethyl ethylenediamine, lysine, ornithine, histidine and arginine. 
   
   
       17 . The method of  claim 9 , further comprising an accelerator selected from the group consisting of N-vinyl pyrrolidinone, 2-vinyl pyridine, 1-vinyl imidazole, 9-vinyl carbazone, 9-vinyl carbozol, acrylic acid, n-vinylcarpolactam, 2-allyl-2-methyl-1,3-cyclopentane dione, and 2-hydroxyethyl acrylate. 
   
   
       18 . The method of  claim 9 , further comprising a viscosity enhancer selected from the group consisting of natural and synthetic polymers. 
   
   
       19 . The method of  claim 9 , where the biological material is selected from the group consisting of neurologic, cardiovascular, hepatic, endocrine, skin, hematopoietic, immune, neurosecretory, metabolic, systemic, and genetic. 
   
   
       20 . The method of  claim 9 , wherein the biological material is from a human.