Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 92, Issue 1, Pages 115-130Publisher
JOHN WILEY & SONS INC
DOI: 10.1002/jps.10279
Keywords
cationic lipid; DNA; hydration; infrared spectroscopy; helper lipid
Funding
- NIGMS NIH HHS [1 R01 GM60587-01] Funding Source: Medline
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM060587] Funding Source: NIH RePORTER
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Infrared spectroscopy was used to examine the effect of dehydration on the structure of DNA and cationic lipid/DNA complexes (CLDCs). Information regarding the effect of hydration on the interface between the cationic lipids and DNA was obtained by following subtle but reproducible changes in vibrational bands arising from the DNAbases and phosphate backbone as well as bands from the lipid ester groups within the interfacial region of the bilayer. Dehydration of supercoiled plasmid DNA induces a transition from a B-conformation in solution to a mixed conformation in the dried state. Changes in vibrations of the bases upon drying suggest a change to an A-conformation whereas vibrations from the phosphate moieties suggest A- or C-forms. Vibrational changes in the ribose ring suggest adoption of a C-conformation. When CLDCs composed of either DOTAP (1,2-dioleoyl-3-trimethylammonium-propane) or DDAB (dioctadecyldimethylammonium bromide) cationic lipids with or without equimolar amounts of the helper lipids cholesterol or DOPE (1,2-dioleoylphosphatidylethanolamin) are dried, the DNA is still able to undergo these structural transitions suggesting a nonrigid CLDC structure. The effect of dehydration on these interfacial interactions was found to be dependent on the type of cationic lipid used as well as the type of helper lipid. In addition, this work provides a simple spectroscopic analytical approach that can be used for the characterization of nonviral vectors that has potential pharmaceutical utility. (C) 2002 Wiley-Liss, Inc.
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