title: Fibrin-lipoplex system for controlled topical delivery of multiple genes.
abstract: Nonviral gene delivery via natural biomacromolecules show great promise as controlled release systems while avoiding the associated drawbacks with viral gene delivery such as immunogenicity and safety issues. Here, a fibrin-lipoplex system for topical delivery of multiple genes is described. In vitro release analysis showed efficient retention of the lipoplexes in the fibrin scaffold. The biomolecular interaction between fibrinogen and liposomes was investigated qualitatively using surface plasmon resonance. The strong binding between the lipoplexes and the fibrinogen component of the scaffold was observed and that could explain the in vitro release profile observed in our studies. Both in vitro and in vivo transfection studies using multiple reporter genes were performed to establish the bioactivity of released lipoplexes. The ability of the lipoplexes to transfect fibroblasts in vitro was shown to be maintained even after extended periods of encapsulation within the scaffold. Furthermore, in a rabbit ear ulcer model, the fibrin-lipoplex system was shown to have significantly higher transfection efficiency for two reporter genes at day 7 when compared to lipoplexes alone, suggesting that this fibrin-lipoplex system is suitable for extended release of lipoplexes for topical gene delivery applications.
authors.affiliation: Network of Excellence for Functional Biomaterials and Regenerative Medicine Institute, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
authors.forename: Mangesh
authors.initials: M
authors.lastname: Kulkarni
authors.forename: Ailish
authors.initials: A
authors.lastname: Breen
authors.forename: Udo
authors.initials: U
authors.lastname: Greiser
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Brien
authors.forename: Abhay
authors.initials: A
authors.lastname: Pandit
mesh_terms: D000287:Administration, Topical; D000818:Animals; D005337:Fibrin; D017930:Genes, Reporter; D005822:Genetic Vectors; D008055:Lipids; D051379:Mice; D041681:NIH 3T3 Cells; D011817:Rabbits; D014162:Transfection
chemical_list: D008055:Lipids; D005337:Fibrin