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Adhesive thermosensitive gels for local delivery of viral vectors
Authors:Jeanette M. Caronia  Daniel W. Sorensen  Hope M. Leslie  Jop H. van Berlo  Samira M. Azarin
Affiliation:1. Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota;2. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota

Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota;3. Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota;4. Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota

Department of Medicine, Cardiovascular Division and Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota;5. Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota

Abstract:
Local delivery of viral vectors can enhance the efficacy of therapies by selectively affecting necessary tissues and reducing the required vector dose. Pluronic F127 is a thermosensitive polymer that undergoes a solution–gelation (sol–gel) transition as temperature increases and can deliver vectors without damaging them. While pluronics can be spread over large areas, such as the surface of an organ, before gelation, they lack sufficient adhesivity to remain attached to some tissues, such as the surface of the heart or mucosal surfaces. Here, we utilized blends of pluronic F127 and polycarbophil (PCB), a mucoadhesive agent, to provide the necessary adhesivity for local delivery of viral vectors to the cardiac muscle. The effects of PCB concentration on adhesive properties, sol–gel temperature transition and cytocompatibility were evaluated. Rheological studies showed that PCB decreased the sol–gel transition temperature at concentrations >1% and increased the adhesive properties of the gel. Furthermore, these gels were able to deliver viral vectors and transduce cells in vitro and in vivo in a neonatal mouse apical resection model. These gels could be a useful platform for delivering viral vectors over the surface of organs where increased adhesivity is required.
Keywords:adhesion  pluronic F127  polycarbophil  solution–gelation transition  viral vector delivery
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