Optimized dextran–polyethylenimine conjugates are efficient non-viral vectors with reduced cytotoxicity when used in serum containing environments

Dahai Jiang; Aliasger K Salem

doi:10.1016/j.ijpharm.2011.10.032

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Optimized dextran–polyethylenimine conjugates are efficient non-viral vectors with reduced cytotoxicity when used in serum containing environments

Journal article

Peer reviewed

Optimized dextran–polyethylenimine conjugates are efficient non-viral vectors with reduced cytotoxicity when used in serum containing environments

Dahai Jiang and Aliasger K Salem

International journal of pharmaceutics, Vol.427(1), pp.71-79

05/01/2012

DOI: 10.1016/j.ijpharm.2011.10.032

PMCID: PMC3295901

PMID: 22037445

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https://www.ncbi.nlm.nih.gov/pmc/articles/3295901View

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Abstract

Polyethylenimine (PEI) is a cationic polymer that is an efficient transfection reagent marred by high toxicity and a susceptibility to aggregate in the presence of serum. Dextran is a biodegradable natural polysaccharide that can be used to reduce the toxicity of PEI and increase its stability in the presence of serum. In this study, small branched PEI units (800/2000Da) were attached to dextran (Dex; 15/100–200kDa) to form dextran–polyethylenimine (Dex–PEI) conjugates. The Dex–PEI conjugates were then tested as a gene carrier in the model HEK293 cell line. Dex–PEI conjugates displayed significantly lower cytotoxicity than PEI (25k). Both Dex–PEI and PEI efficiently delivered firefly luciferase encoded plasmid DNA (pDNA) to the HEK293 cells. Dex–PEI resulted in moderately lower transfection efficiencies than PEI 25k when the transfection was carried out in media without serum for 4h. However, in the presence of serum, which more accurately predicts the anticipated environment of non-viral vectors in vivo, Dex–PEI and unmodified PEI generated similar transfection efficiencies when incubated with the cells for 4h. When the incubation time of the vectors was increased to 48h, significantly higher transfection efficiencies were generated by Dex–PEI in comparison to PEI. Turbidity measurements showed that complexes formed between plasmid DNA and unmodified PEI were more susceptible to aggregation in serum-containing media than complexes formed from pDNA and Dex–PEI. Dex–PEI conjugates are therefore believed to have greater potential for translational applications because of lower cytotoxicity characteristics and improved stability in serum containing environments.

Complexes

Non-viral

Dextran

Nanoparticles

Gene delivery

Polyethylenimine

Nanoplexes

Transfection

pDNA

PEI

Cationic polymer

Serum

Plasmid DNA

Details

Title: Subtitle: Optimized dextran–polyethylenimine conjugates are efficient non-viral vectors with reduced cytotoxicity when used in serum containing environments
Creators: Dahai Jiang
Aliasger K Salem
Resource Type: Journal article
Publication Details: International journal of pharmaceutics, Vol.427(1), pp.71-79
DOI: 10.1016/j.ijpharm.2011.10.032
PMID: 22037445
PMCID: PMC3295901
NLM abbreviation: Int J Pharm
ISSN: 0378-5173
eISSN: 1873-3476
Publisher: Elsevier B.V
Language: English
Date published: 05/01/2012
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9983986522302771

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