International Journal of Pharmaceutics 2014-10-20

Bis-quaternary gemini surfactants as components of nonviral gene delivery systems: a comprehensive study from physicochemical properties to membrane interactions.

Ana M Cardoso, Catarina M Morais, Sandra G Silva, Eduardo F Marques, Maria C Pedroso de Lima, Maria Amália S Jurado

Index: Int. J. Pharm. 474(1-2) , 57-69, (2014)

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Abstract

Gemini surfactants have been successfully used as components of gene delivery systems. In the present work, a family of gemini surfactants, represented by the general structure [CmH2m+1(CH3)2N(+)(CH2)sN(+)(CH3)2CmH2m+1]2Br(-), or simply m-s-m, was used to prepare cationic gene carriers, aiming at their application in transfection studies. An extensive characterization of the gemini surfactant-based complexes, produced with and without the helper lipids cholesterol and DOPE, was carried out in order to correlate their physico-chemical properties with transfection efficiency. The most efficient complexes were those containing helper lipids, which, combining amphiphiles with propensity to form structures with different intrinsic curvatures, displayed a morphologically labile architecture, putatively implicated in the efficient DNA release upon complex interaction with membranes. While complexes lacking helper lipids were translocated directly across the lipid bilayer, complexes containing helper lipids were taken up by cells also by macropinocytosis. This study contributes to shed light on the relationship between important physico-chemical properties of surfactant-based DNA vectors and their efficiency to promote gene transfer, which may represent a step forward to the rational design of gene delivery systems.Copyright © 2014 Elsevier B.V. All rights reserved.