Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1838, Issue 1, Pages 398-412Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2013.09.008
Keywords
CL-DNA; Lipoplex; Salt; Steric stabilization; SAXS; Gene therapy
Categories
Funding
- NSF [DMR-1101900]
- DOE-BES [DE-FG02-06ER46314]
- NIH [GM-59288]
- Marie Curie International Outgoing Fellowship
- Swedish Research Council
- Ministry of Education, Science and Technology [R33-2008-000-10163-0]
- MRSEC Program of the NSF [DMR-1121053]
- NSF
- [PIOF-GA-2009252701]
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1101900] Funding Source: National Science Foundation
- U.S. Department of Energy (DOE) [DE-FG02-06ER46314] Funding Source: U.S. Department of Energy (DOE)
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Cationic liposome-DNA (CL-DNA) complexes, are regarded as promising materials for safe and efficient delivery of genes for therapeutical applications. In order to be used in vivo, these complexes may be coated with a hydrophilic polymer (e.g. polyethylene-glycol, PEG) that provides steric stabilization towards adhesion of proteins and removal by the immune system. In this work we study the influence of the initial salt concentration (Cs) - which modulates the electrostatic interaction between oppositely charged vesicles and DNA - on the structure and stability of PEGylated CL-DNA particles. Previous small-angle X-ray scattering has shown that if non-PEGylated or PEGylated CL-DNA lamellar complexes are prepared in water, their structure is well defined with a high number of lipid membrane-DNA layers (larger than 20). Here we show that if these complexes are transferred to saline media (150 mM NaCI or DMEM, both near physiological conditions), this structure remains nearly unchanged. Conversely, if PEGylated complexes are prepared in saline media, their lamellar structure is much looser, with fewer number of layers. This pathway dependent behavior of PEGylated complex formation in brine is modulated by the liposome membrane charge density and the mole fraction of PEG 2000 in the membranes, with the average number of layers decreasing with increasing Cs and in going from 5 mol% to 10 mol% PEG-lipid. Each of these structures (high and low number of layers) is stable with time, suggesting that despite complex formation being thermodynamically favored, the complexation process in PEGylated membranes, which determines the number of layers per particle, is kinetically controlled. In the extreme case (when polymer repulsions from 10 mol% PEG-lipid are maximized and electrostatic attraction between PEGylated CLs and DNA are minimized at low membrane charge density) complex formation is suppressed at high Cs = 150 mM. (C) 2013 Elsevier B.V. All rights reserved.
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