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Exploring the Correlation Between Lipid Packaging in Lipoplexes and Their Transfection Efficacy
School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK
* Author to whom correspondence should be addressed.
Received: 15 September 2011; in revised form: 7 November 2011 / Accepted: 10 November 2011 / Published: 18 November 2011
Abstract: Whilst there is a large body of evidence looking at the design of cationic liposomes as transfection agents, correlates of formulation to function remain elusive. In this research, we investigate if lipid packaging can give further insights into transfection efficacy. DNA lipoplexes composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) in combination with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-stearoyl-3-trimethylammonium-propane (DSTAP) were prepared by the lipid hydration method. Each of the formulations was prepared by hydration in dH2O or phosphate buffer saline (PBS) to investigate the effect of buffer salts on lipoplex physicochemical characteristics and in vitro transfection. In addition, Langmuir monolayer studies were performed to investigate any possible correlation between lipid packaging and liposome attributes. Using PBS, rather than dH2O, to prepare the lipoplexes increased the size of vesicles in most of formulations and resulted in variation in transfection efficacies. However, one combination of lipids (DSPE:DOTAP) could not form liposomes in PBS, whilst the DSPE:DSTAP combination could not form liposomes in either aqueous media. Monolayer studies demonstrated saturated lipid combinations offered dramatically closer molecular packing compared to the other combinations which could suggest why this lipid combination could not form vesicles. Of the lipoplexes prepared, those formulated with DSTAP showed higher transfection efficacy, however, the effect of buffer on transfection efficiency was formulation dependent.
Keywords: Langmuir studies; lipid packaging; cationic liposomes; gene delivery; transfection; electrolytes
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Moghaddam, B.; McNeil, S.E.; Zheng, Q.; Mohammed, A.R.; Perrie, Y. Exploring the Correlation Between Lipid Packaging in Lipoplexes and Their Transfection Efficacy. Pharmaceutics 2011, 3, 848-864.
Moghaddam B, McNeil SE, Zheng Q, Mohammed AR, Perrie Y. Exploring the Correlation Between Lipid Packaging in Lipoplexes and Their Transfection Efficacy. Pharmaceutics. 2011; 3(4):848-864.
Moghaddam, Behfar; McNeil, Sarah E.; Zheng, Qinguo; Mohammed, Afzal R.; Perrie, Yvonne. 2011. "Exploring the Correlation Between Lipid Packaging in Lipoplexes and Their Transfection Efficacy." Pharmaceutics 3, no. 4: 848-864.