Injectable, Guest–Host Assembled Polyethylenimine Hydrogel for siRNA Delivery | Zendy

Leo Wang | Zendy; Jan. Sloand | Zendy; Ann C. Gaffey | Zendy; Chantel M. Venkataraman | Zendy; Zhichun Wang | Zendy; Alen Trubelja | Zendy; Daniel A. Hammer | Zendy; Pavan Atluri | Zendy; Jason A. Burdick | Zendy

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Injectable, Guest–Host Assembled Polyethylenimine Hydrogel for siRNA Delivery

Author(s) -

Leo Wang,

Jan. Sloand,

Ann C. Gaffey,

Chantel M. Venkataraman,

Zhichun Wang,

Alen Trubelja,

Daniel A. Hammer,

Pavan Atluri,

Jason A. Burdick

Publication year - 2016

Publication title -

biomacromolecules

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.689

H-Index - 220

eISSN - 1526-4602

pISSN - 1525-7797

DOI - 10.1021/acs.biomac.6b01378

Subject(s) - polyethylenimine , gene silencing , transfection , small interfering rna , self healing hydrogels , chemistry , polyethylene glycol , biophysics , rna interference , peg ratio , green fluorescent protein , microbiology and biotechnology , rna , biochemistry , polymer chemistry , biology , gene , finance , economics

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.

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