Document Detail

Functionalized, biodegradable hydrogels for control over sustained and localized siRNA delivery to incorporated and surrounding cells.
MedLine Citation:
PMID:  22902819     Owner:  NLM     Status:  MEDLINE    
Currently, the most severe limitation to applying RNA interference technology is delivery, including localizing the molecules to a specific site of interest to target a specific cell population and sustaining the presentation of these molecules for a controlled period of time. In this study, we engineered a functionalized, biodegradable system created by covalent incorporation of cationic linear polyethyleneimine (LPEI) into photocrosslinked dextran (DEX) hydrogels through a biodegradable ester linkage. The key innovation of this system is that control over the sustained release of short interference RNA (siRNA) was achieved, as LPEI could electrostatically interact with siRNA to maintain siRNA within the hydrogels and degradation of the covalent ester linkages between the LPEI and the hydrogels led to tunable release of LPEI/siRNA complexes over time. The covalent conjugation of LPEI did not affect the swelling or degradation properties of the hydrogels, and the addition of siRNA and LPEI had minimal effect on their mechanical properties. These hydrogels exhibited low cytotoxicity against human embryonic kidney 293 cells (HEK293). The release profiles could be tailored by varying DEX (8 and 12% w/w) and LPEI (0, 5, 10 μg/100 μl gel) concentrations with nearly 100% cumulative release achieved at day 9 (8% w/w gel) and day 17 (12% w/w gel). The released siRNA exhibited high bioactivity with cells surrounding and inside the hydrogels over an extended time period. This controllable and sustained siRNA delivery hydrogel system that permits tailored siRNA release profiles may be valuable to guide cell fate for regenerative medicine and other therapeutic applications such as cancer treatment.
Khanh Nguyen; Phuong Ngoc Dang; Eben Alsberg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-16
Journal Detail:
Title:  Acta biomaterialia     Volume:  9     ISSN:  1878-7568     ISO Abbreviation:  Acta Biomater     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-26     Completed Date:  2013-06-11     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  101233144     Medline TA:  Acta Biomater     Country:  England    
Other Details:
Languages:  eng     Pagination:  4487-95     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ltd.
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MeSH Terms
Biocompatible Materials*
Dextrans / chemistry
HEK293 Cells
Magnetic Resonance Spectroscopy
Polyethyleneimine / chemistry
RNA, Small Interfering / administration & dosage*
Grant Support
Reg. No./Substance:
0/Biocompatible Materials; 0/Hydrogels; 0/RNA, Small Interfering; 9002-98-6/Polyethyleneimine; K3R6ZDH4DU/Dextrans

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