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    
Abstract/OtherAbstract:
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.
Authors:
Khanh Nguyen; Phuong Ngoc Dang; Eben Alsberg
Related Documents :
25405589 - Solution-processed parallel tandem polymer solar cells using silver nanowires as interm...
10072769 - Selection of cdnas encoding putative type ii membrane proteins on the cell surface from...
7649259 - Biosynthesis and apical localization of the urokinase receptor in polarized mdck epithe...
22783109 - Occurrence of clubroot on shepherd's-purse caused by plasmodiophora brassicae.
3886789 - Mutant el-4 thymoma cells polyclonally activate murine and human b cells via direct cel...
1847659 - Malignant transformation of human fibroblasts correlates with increased activity of rec...
11559769 - Heterogeneous expression of the delayed-rectifier k+ currents i(k,r) and i(k,s) in rabb...
8103779 - Hippocampal regulation of the survival and morphological development of locus coeruleus...
16557809 - Cellular responses of mice to diffusion chambers i. reactions to intraperitoneal diffus...
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.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Biocompatible Materials*
Dextrans / chemistry
HEK293 Cells
Humans
Hydrogels*
Kinetics
Magnetic Resonance Spectroscopy
Polyethyleneimine / chemistry
RNA, Small Interfering / administration & dosage*
Rheology
Transfection
Grant Support
ID/Acronym/Agency:
R21DE022376/DE/NIDCR NIH HHS; R56 DE022376/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Biocompatible Materials; 0/Hydrogels; 0/RNA, Small Interfering; 9002-98-6/Polyethyleneimine; K3R6ZDH4DU/Dextrans
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Pro-angiogenic CD14(++) CD16(+) CD163(+) monocytes accelerate the in vitro endothelialisation of sof...
Next Document:  Osteogenic and angiogenic potentials of monocultured and co-cultured human-bone-marrow-derived mesen...