title: Injectable, Guest-Host Assembled Polyethylenimine Hydrogel for siRNA Delivery.
abstract: While siRNA has tremendous potential for therapeutic applications, advancement is limited by poor delivery systems. Systemically, siRNAs are rapidly degraded, may have off-target silencing, and necessitate high working concentrations. To overcome this, we developed an injectable, guest-host assembled hydrogel between polyethylenimine (PEI) and polyethylene glycol (PEG) for local siRNA delivery. Guest-host modified polymers assembled with siRNAs to form polyplexes that had improved transfection and viability compared to PEI. At higher concentrations, these polymers assembled into shear-thinning hydrogels that rapidly self-healed. With siRNA encapsulation, the assemblies eroded as polyplexes which were active and transfected cells, observed by Cy3-siRNA uptake or GFP silencing in vitro. When injected into rat myocardium, the hydrogels localized polyplex release, observed by uptake of Cy5.5-siRNA and silencing of GFP for 1 week in a GFP-expressing rat. These results illustrate the potential for this system to be applied for therapeutic siRNA delivery, such as in cardiac pathologies.
authors.affiliation: Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Leo L
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Janna N
authors.initials: JN
authors.lastname: Sloand
authors.affiliation: Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Gaffey
authors.affiliation: Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Chantel M
authors.initials: CM
authors.lastname: Venkataraman
authors.affiliation: Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Alen
authors.initials: A
authors.lastname: Trubelja
authors.affiliation: Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hammer
authors.affiliation: Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Pavan
authors.initials: P
authors.lastname: Atluri
authors.affiliation: Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Jason A
authors.identifier: 0000-0002-2006-332X
authors.initials: JA
authors.lastname: Burdick
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011108:Polymers; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011094:Polyethyleneimine