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Injectable, Guest-Host Assembled Polyethylenimine Hydrogel for siRNA Delivery
Leo L Wang1, Janna N Sloand1, Ann C Gaffey1
1Department of Bioengineering, ‡Division of Cardiovascular Surgery, Department of Surgery, and §Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.
Biomacromolecules
|December 21, 2016
Summary
This study presents a novel hydrogel for effective local delivery of small interfering RNA (siRNA) therapeutics. The developed hydrogel system enhances siRNA transfection and silencing in cardiac tissue, overcoming current delivery challenges.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Nanotechnology
Background:
- Small interfering RNA (siRNA) holds therapeutic promise but faces limitations due to poor delivery systems, including rapid degradation and off-target effects.
- Effective delivery of siRNA requires overcoming challenges like systemic degradation and the need for high concentrations.
Purpose of the Study:
- To develop an injectable hydrogel system for localized siRNA delivery, improving therapeutic efficacy and overcoming current delivery limitations.
- To create a guest-host assembled hydrogel using polyethylenimine (PEI) and polyethylene glycol (PEG) for enhanced siRNA transfection and viability.
Main Methods:
- Developed a guest-host modified polymer system that self-assembles with siRNA into polyplexes.
- Formulated injectable, shear-thinning, and self-healing hydrogels capable of encapsulating siRNA.
- Evaluated in vitro transfection efficiency and cell viability, and in vivo siRNA delivery and gene silencing in rat myocardium.
Main Results:
- The guest-host modified polymers formed polyplexes with improved transfection and viability compared to PEI alone.
- Encapsulated siRNA within hydrogels resulted in active polyplex release and demonstrated effective gene silencing in vitro.
- In vivo studies showed localized polyplex release and sustained GFP silencing for one week in rat myocardium.
Conclusions:
- The developed injectable hydrogel system offers a promising platform for localized therapeutic siRNA delivery.
- This technology has potential applications in treating various conditions, particularly cardiac pathologies, by enhancing siRNA efficacy and safety.
