title: Engineering a polymeric gene delivery vector based on poly(ethylenimine) and hyaluronic acid.
abstract: In this work, the effects of primary amines, ligand targeting, and overall charge on the effectiveness of branched poly(ethylenimine)-hyaluronic acid conjugate (bPEI-HA) zwitterionic gene delivery vectors are investigated. To elucidate the relative importance of each of these parameters, we explored the zeta potential, cytotoxicity, and transfection efficiency for a variety of formulations of bPEI-HA. It was found that the length of the hyaluronic acid (HA) oligosaccharide had the most significant effect on cytotoxicity and transfection efficiency with human mesenchymal stem cells. Test groups of bPEI incorporating HA with a length of 10 saccharides had significantly higher transfection efficiency (14.6 ± 2.0%) and lower cytotoxicity than other formulations tested, with the cytotoxicity of the group containing the greatest mass of 10 saccharide showing similar results as the positive controls at the highest polymer concentration (100 μg/mL). Additionally, molar incorporation of HA, as opposed to the saccharide length and HA mass incorporation, had the greatest effect on zeta potential but a minor effect on both cytotoxicity and transfection efficiency. This work demonstrates the relative importance of each of these tunable design criteria when creating a zwitterionic polymeric gene delivery vector and provides useful specific information regarding the design of bPEI-HA gene delivery vectors.
authors.affiliation: Department of Bioengineering, Rice University, 6100 Main Street, Houston, Texas 77005, USA.
authors.forename: Clark J
authors.initials: CJ
authors.lastname: Needham
authors.forename: Austin K
authors.initials: AK
authors.lastname: Williams
authors.forename: Sue Anne
authors.initials: SA
authors.lastname: Chew
authors.forename: F Kurtis
authors.initials: FK
authors.lastname: Kasper
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D011094:Polyethyleneimine / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004337:Drug Carriers; D011094:Polyethyleneimine; D006820:Hyaluronic Acid