Injectable, Guest–Host Assembled Polyethylenimine Hydrogel for siRNA Delivery

Wang, Leo L.; Sloand, Janna N.; Gaffey, Ann C.; Venkataraman, Chantel M.; Wang, Zhichun; Trubelja, Alen; Hammer, Daniel A.; Atluri, Pavan; Burdick, Jason A.

doi:10.1021/acs.biomac.6b01378

Injectable, Guest–Host Assembled Polyethylenimine Hydrogel for siRNA Delivery

Journal Article · Sun Dec 04 23:00:00 EST 2016 · Biomacromolecules

DOI:https://doi.org/10.1021/acs.biomac.6b01378· OSTI ID:1534427

Wang, Leo L. ^[1]; Sloand, Janna N. ^[2]; Gaffey, Ann C. ^[2]; Venkataraman, Chantel M. ^[2]; Wang, Zhichun ^[2]; Trubelja, Alen ^[2]; Hammer, Daniel A. ^[2]; Atluri, Pavan ^[2]; ^[2]

Univ. of Pennsylvania, Philadelphia, PA (United States); DOE/OSTI
Univ. of Pennsylvania, Philadelphia, PA (United States)

While siRNA has immense 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.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Pennsylvania, Philadelphia, PA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); American Heart Association (AHA); National Institutes of Health (NIH); National Science Foundation (NSF); USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division

Grant/Contract Number:: SC0007063

OSTI ID:: 1534427

Journal Information:: Biomacromolecules, Journal Name: Biomacromolecules Journal Issue: 1 Vol. 18; ISSN 1525-7797

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Injectable, Guest–Host Assembled Polyethylenimine Hydrogel for siRNA Delivery

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