Exploring the correlation between lipid packaging in lipoplexes and their transfection efficacy

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.

Publication DOI: https://doi.org/10.3390/pharmaceutics3040848
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: Creative commons : Attribution
Uncontrolled Keywords: cationic liposomes,electrolytes,gene delivery,langmuir studies,lipid packaging,transfection,Pharmaceutical Science
Publication ISSN: 1999-4923
Last Modified: 04 Jan 2024 08:16
Date Deposited: 10 Oct 2013 09:24
Full Text Link: http://www.mdpi ... 99-4923/3/4/848
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2011-11-18
Authors: Moghaddam, Behfar
McNeil, Sarah E.
Zheng, Qinguo (ORCID Profile 0000-0001-6351-4082)
Mohammed, Afzal R. (ORCID Profile 0000-0002-5212-3040)
Perrie, Yvonne

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License: Creative Commons Attribution


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