Journal article
Metabolic stability of glutaraldehyde cross‐linked peptide dna condensates
Journal of pharmaceutical sciences, Vol.88(8), pp.739-746
08/1999
DOI: 10.1021/js990042p
PMID: 10430535
Abstract
The stability of peptide DNA condensates was examined after introducing glutaraldehyde to cross‐link surface amine groups. A 20 amino acid peptide (CWK18) was used to condense DNA into small (70 nm) condensates. The reaction between glutaraldehyde and peptide DNA condensates was indirectly monitored using a fluorescence‐based assay to establish reaction completion in 4–5 h when using glutaraldehyde‐to‐peptide ratios of 1 to 4 mol equiv. Higher levels of glutaraldehyde cross‐linking led to significant increases in particle size. The improved stability imparted by glutaraldehyde cross‐linking was demonstrated by the increased resistance of DNA condensates to shear stress induced fragmentation. The cross‐linked condensates were also significantly more resistant to in vitro metabolism by serum endonucleases. A decrease in the magnitude of transient gene expression was determined for cross‐linked DNA condensates which also resulted in a 10‐day steady‐state expression when cross‐linking with 4 mol equiv of glutaraldehyde. The results suggest that cross‐linking DNA condensates may provide a means to alter the time course of transient gene expression by inhibiting DNA metabolism.
Details
- Title: Subtitle
- Metabolic stability of glutaraldehyde cross‐linked peptide dna condensates
- Creators
- Roger C Adami - Division of Pharmaceutics, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109‐1065Kevin G Rice - Division of Pharmaceutics, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109‐1065
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical sciences, Vol.88(8), pp.739-746
- DOI
- 10.1021/js990042p
- PMID
- 10430535
- NLM abbreviation
- J Pharm Sci
- ISSN
- 0022-3549
- eISSN
- 1520-6017
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 08/1999
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065310902771
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