Enhancements in Gene Expression by the Choice of Plasmid DNA Formulations Containing Neutral Polymeric Excipients
Formulations containing maltodextrin (2% w/v) were identified to facilitate intramuscular (im) delivery of plasmid DNA in mice using the reporter genes luciferase and chloramphenicol acetyltransferase (CAT) and the therapeutic gene of erythropoietin (EPO) as monitors of transfection efficiency. Even...
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Published in | Journal of pharmaceutical sciences Vol. 91; no. 5; pp. 1371 - 1381 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Elsevier Inc
01.05.2002
Wiley Subscription Services, Inc., A Wiley Company Wiley American Pharmaceutical Association |
Subjects | |
Online Access | Get full text |
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Summary: | Formulations containing maltodextrin (2% w/v) were identified to facilitate intramuscular (im) delivery of plasmid DNA in mice using the reporter genes luciferase and chloramphenicol acetyltransferase (CAT) and the therapeutic gene of erythropoietin (EPO) as monitors of transfection efficiency. Even though considerable variability in gene expression was observed in animals, a 5–8-fold enhancement of reporter gene expression was observed with this excipient compared with saline formulations of DNA. In a therapeutically significant experiment, a single im injection of an EPO plasmid formulation containing 2% (w/v) maltodextrin resulted in a significant and prolonged elevation of the hematocrit levels of mice compared with control DNA in saline. Biophysical studies with Fourier transform infrared (FTIR) spectroscopy, isothermal titration, and differential scanning calorimetry (DSC) suggested a weak interaction between DNA and maltodextrin as well as a thermal stabilizing effect on the DNA. These in vivo and biophysical results with maltodextrin are comparable to those reported previously with other nonionic polymers, such as poly(vinyl pyrrolidone) and poloxamers, and indicate that maltodextrin is an additional nonionic excipient that displays the property of gene expression enhancement. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 1371–1381, 2002 |
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Bibliography: | ark:/67375/WNG-NCLHFWPP-Q ArticleID:JPS10130 istex:F71D32115A4E8EDD894C17FE5F649F55E55B239D ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3549 1520-6017 |
DOI: | 10.1002/jps.10130 |