Document Detail


Stability of poly(L-lysine)-complexed plasmid DNA during mechanical stress and DNase I treatment.
MedLine Citation:
PMID:  10578502     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to investigate the formation and stability of complexes between plasmid DNA (pDNA) and poly(L-lysine) (PLL). Formation of pDNA/PLL complexes with various ratios was determined by a fluorescence spectrophotometric method using fluorescamine. The effects of sonication, vortexing, and exposure to DNase I on the stability of free pDNA and pDNA/PLL complexes are discussed. A linear correlation between PLL added and PLL bound was obtained with overall reaction efficiency of 84.2-92.6%. Sonication degraded both free and PLL-complexed pDNA within 15 sec of vortexing. However, vortexing did not alter the stability of free and complexed pDNA. Dramatic increase in the protection of pDNA in pDNA/PLL complexes was observed in the DNase I digestion experiment; 68.1-89.0% of total pDNA in the pDNA/PLL complexes was protected from DNase I digestion compared to only 19.2% of total pDNA that remained undegraded after DNase I treatment of free pDNA. An increase in the PLL/pDNA ratio led to an increase in the protection of supercoiled pDNA; 15.5-38.2% of supercoiled pDNA pin PLL/pDNA complexes was protected after DNase I treatment. The results show that complexation of pDNA with PLL can stabilize the supercoiled structure of pDNA for the development of biodegradable microspheres as a delivery system for pDNA. Stability of pDNA/PLL complex can be monitored by PicoGreen dye and fluorescence densitometric assay methods.
Authors:
Y Capan; B H Woo; S Gebrekidan; S Ahmed; P P DeLuca
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmaceutical development and technology     Volume:  4     ISSN:  1083-7450     ISO Abbreviation:  Pharm Dev Technol     Publication Date:  1999  
Date Detail:
Created Date:  2000-01-19     Completed Date:  2000-01-19     Revised Date:  2006-05-01    
Medline Journal Info:
Nlm Unique ID:  9610932     Medline TA:  Pharm Dev Technol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  491-8     Citation Subset:  IM    
Affiliation:
University of Kentucky, College of Pharmacy, Faculty of Pharmaceutical Sciences, Lexington 40536, USA.
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MeSH Terms
Descriptor/Qualifier:
DNA / chemistry*
Densitometry
Deoxyribonuclease I / chemistry*
Drug Stability
Electrophoresis, Agar Gel
Fluorescent Dyes
Organic Chemicals
Plasmids / chemistry*
Polylysine / chemistry*
Solutions
Spectrometry, Fluorescence
Stress, Mechanical*
Ultrasonics
Chemical
Reg. No./Substance:
0/Fluorescent Dyes; 0/Organic Chemicals; 0/PicoGreen; 0/Solutions; 25104-18-1/Polylysine; 9007-49-2/DNA; EC 3.1.21.1/Deoxyribonuclease I

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


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