title: A novel method to enhance the stability of alginate-poly-L-lysine-alginate microcapsules.
abstract: Implantation of microencapsulated recombinant cells is an alternative approach to gene therapy. These genetically-engineered cells enclosed in microcapsules to deliver therapeutic recombinant products have been effective in treating several murine models of human diseases. However, the most commonly used microcapsules fabricated from alginate ionically cross-linked with calcium suffer from loss of long-term mechanical stability. We now report on a method to improve their stability by introducing additional polymers to provide covalent linkages via photopolymerization. Vinyl monomers and a photoinitiator were allowed to diffuse into the initially formed calcium-alginate microcapsules. In situ photopolymerization in the presence of sodium acrylate and N-vinylpyrrolidone substantially enhanced their mechanical strength. After four months of storage in saline, > 70% of these capsules remained intact in the osmotic pressure test, while the un-modified alginate microcapsules totally disintegrated. Tests of their permeability to polyethylene glycol of different molecular weight and their ability to support cell survival showed that these properties remained unaffected by the photopolymerization. Hence, these microcapsules modified by adding a network of vinyl polymers are promising candidates to use for long-term delivery of recombinant gene products in this cell-based method of gene therapy.
authors.affiliation: Department of Chemistry, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Maggie S
authors.initials: MS
authors.lastname: Wang
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Childs
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Chang
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002214:Capsules / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival; D019343:Citric Acid; D005782:Gels / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D051379:Mice; D011107:Polylysine / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry; D012996:Solutions; D013718:Tensile Strength; D013997:Time Factors
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D005782:Gels; D006603:Hexuronic Acids; D011760:Pyrrolidinones; D012996:Solutions; D011107:Polylysine; D019343:Citric Acid; D020723:Glucuronic Acid