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.
Bibliographical noteFunding Information:
Jeanette Caronia was supported by a Biotechnology Training Grant (NIH T32GM008347). Daniel Sorensen was supported by a Stem Cell Biology Training Grant (NIH T32GM113846). J.H.v.B. and S.M.A were supported by Regenerative Medicine Minnesota grant RMM102516009. J.H.v.B. is supported by an Individual Biomedical Research Award from The Hartwell Foundation. The authors would like to thank Ghaidan Shamsan and Dr. David Odde for assistance on the Nikon Tie2 microscope for the in vitro transduction studies. Part of this study was carried out in the College of Science and Engineering Polymer Characterization Facility, University of Minnesota, which has received capital equipment funding from the NSF through the UMN MRSEC program under Award Number DMR-1420013.
- pluronic F127
- solution–gelation transition
- viral vector delivery