Injectable, Guest-Host Assembled Polyethylenimine Hydrogel for siRNA Delivery.
Publication/Presentation Date
1-9-2017
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.
Volume
18
Issue
1
First Page
77
Last Page
86
ISSN
1526-4602
Published In/Presented At
Wang, L. L., Sloand, J. N., Gaffey, A. C., Venkataraman, C. M., Wang, Z., Trubelja, A., Hammer, D. A., Atluri, P., & Burdick, J. A. (2017). Injectable, Guest-Host Assembled Polyethylenimine Hydrogel for siRNA Delivery. Biomacromolecules, 18(1), 77–86. https://doi.org/10.1021/acs.biomac.6b01378
Disciplines
Medicine and Health Sciences
PubMedID
27997133
Department(s)
Department of Surgery
Document Type
Article