Lipoplexes nucleic acid release

Mechanism of Nucleic Acid Release from Lipoplexes. 74... 

Cationic lipids interact electrostatically and form stable complexes (lipoplexes) with the polyanionic nucleic acids. The structure of most lipoplexes is a multi-lamellar sandwich in which lipid bilayers alternate with layers of DNA strands [16, 62-64] (Fig. 20). Although infrequent, nonlamellar structures have also been found. The free energy gain upon lipoplex formation was shown to be essentially of entropic nature resulting from the counterion release and macromolecule dehydration [65, 66]. 

Lipoplexes are prepared by the interaction of anionic nucleic acids with the surface of cationic lipid to afford multilamellar lipid-nucleic acid complexes. Cationic liposomes can protect nucleic acids from serum nucleases and facilitate the cellular uptake and release of nucleic acids into the cytosol [218]. Pedroso et al. [219] have extensively discussed the structure-activity relationships of cationic lipo-some/DNA complexes and the key formulation parameters influencing the properties of lipoplexes. In addition, optimization of the cationic liposomal complexes for in vivo application has been reviewed by Smyth [220]. 

Figure 7.3-2. Matrix-based DNA delivery can be divided into encapsulation and release approaches, where the nucleic acid is encapsulated for later release, and matrix-tethered delivery, where nucleic acid polyplexes or lipoplexes are immobilized directly to a matrix that also supports cell adhesion. These approaches are typically used for applications in tissue engineering where the delivery of nucleic acids is used to augment tissue formation.

Other research aimed at capitalizing npon the acidification events within the endosomes to prompt endosomal escape and DNA release involved the incorporation of histidine moieties into gene delivery vectors. Histidine was previonsly incorporated into polymers and showed both an ability to dismpt endosomes and good transfection results." This led to the development by Chaudhuri et al. of a library of neutral or cationic amphiphiles with histidine moieties to impart pH sensitivity to their Upoplex systems. The goal of these systems was to enhance transfection efficiencies by creating lipoplexes that wonld strongly associate with nucleic acids, prevent inactivation of the complex due to serum adsorption, and facilitate endosomal destabilization. 

Liposomes are vesicles with a bilayer lipid sheet formed by cationic lipids in aqueous solutions. When liposomes get in contact with nucleic acids they undergo a rearrangement into nucleic acid lipid complexes called lipoplexes. Lipoplexes can be actively taken up by eukaryotic cells by endocytosis, and the lipoplex is then internalized into the cell cytosol within endosomes. The endo-somal complex is finally destroyed by increasing the osmotic pressure created by the lipids buffering action and by the fusion of the lipid with the endosomal membrane. The ability of a lipid to destroy endosomes, also referred to as endosomal escape, is one of the main characteristics of a good synthetic transfection reagent, as it indicates the capability of the vector to release its nncleic acid load into cells once having crossed the cell membrane. 

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