Cationic Liposomes for Gene Delivery: From Biophysics to Biological Applications

Abstract

The use of an efficient carrier for nucleic acid-based medicines is considered to be a determinant factor for the successful application of gene therapy. The drawbacks associated with the use of viral vectors, namely those related with safety problems, have prompted investigators to develop alternative methods for gene delivery, cationic lipid-based systems being the most representative. Despite extensive research in the last decade on the use of cationic liposomes as gene transfer vectors and the development of elegant strategies to enhance their biological activity, these systems are still far from being viable alternatives to the use of viral vectors in gene therapy. In this review considerations are made regarding the structure-activity relationships of cationic liposome/DNA complexes and the key formulation parameters influencing the features of lipoplexes are presented and discussed in terms of their effect on biological activity. Particular emphasis is given to the interaction of the lipoplexes with serum components as well as to novel strategies developed to circumvent difficulties that may emerge upon iv administration of the complexes. Finally, since the ability of the lipoplexes to be stored while preserving their transfection activity is a crucial issue for the repeated use of such carriers, approaches reported on the improvement of their physical stability are also reviewed.

Design and evaluation of new pH-sensitive amphiphilic cationic lipids for siRNA delivery

“…In general, the transfection efficiency of cationic lipid carriers has been shown to decrease with increasing alkyl chain length and saturation [26]. When saturated, shorter aliphatic chains (C 12 and C 14 ) favor higher rates of inter-membrane lipid mixing and reportedly allow for better transfection efficiencies in vitro , as compared to in vivo , whereas the opposite is true for longer chains (C 16 and C 18 ) [17,27].…”

“…Typically, saturated fatty acids greater than 14 carbons in length are not favorable for nucleic acid transfections due to their elevated phase transition temperature and overall less fluidity than those that are unsaturated [28]. However, it has been discovered that there exists a limit, at which point an increase in unsaturation and lipid fluidity is inversely correlated to transfection efficiency, primarily because some degree of rigidity is required for particle stability, as evidenced by the widespread use of cholesterol in lipid nanoparticle formulations [26,29]. …”

N4,N9-Dioleoyl Spermine Is a Novel Nonviral Lipopolyamine Vector for Plasmid DNA Formulation

“…These unsaturated chains are linked by amide bonds at the secondary amino groups of spermine to form N 4 ,N 9 -dioleoyl spermine (commercially available as LipoGen) (32). These amide linkers have the advantages of being both biodegradable and less toxic than the ether bonds in DOTMA (33,34). The ability of this synthetic lipopolyamine to condense DNA was studied using ethidium bromide (EthBr) fluorescence quenching and light scattering assays.…”

Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs

“…The association of nucleotides and cationic lipids to multimolecular structures is a highly complex process that is poorly understood so far. 41,42 The specific nature of the cationic lipid involved, the presence and sort of helper lipids, the salt conditions and even the sequence of addition of lipids and nucleotides appear to influence the nature of the nucleotide-lipid complexes. Obviously, the charge ratio is also of major importance.…”