Lipid polycationic

Hong S, Leroueil PR, Janus EK, et al. (2006). Interaction of polycationic polymers with supported lipid bilayers and cells nanoscale hole formation and enhanced membrane permeability. Bioconjug. Chem. 17 728-34. 

The structure of a cationic lipid can be broken-down into three structural elements a lipophilic lipid anchor comprising one or—mostly—two long alkyl chains or Choi, a spacer, and a polar, positively charged head group consisting of one or more quaternised or protonatable amino groups. Figure 2 shows a few of the well-known, older cationic lipids, which can be classified as either monocationic or polycationic lipids. A series of recently synthesized cationic lipids will be discussed later. 

The intracellular trafficking pathway of plasmid DNA complexed by polycationic lipid 192... 

Abstract In the late 1980s independent work by Feigner and Behr pioneered the use of cationic materials to complex and deliver nucleic acids into eukaryotic cells. Since this time, a vast number of synthetic transfection vectors, which are typically divided into two main transfectors , have been developed namely (1) cationic lipids and (2) polycationic polymers. In this chapter the main synthetic approaches used for the synthesis of these compounds will be reviewed with particular attention paid to cationic lipids and dendrimers. This review is aimed primarily at the younger audience of doctoral students and non-specialist readers. 

The first reports of using cationic polymers for DNA delivery can be traced back to 1973, before the use of cationic lipids. However, until recently, research in the area of polymer-mediated gene delivery lagged behind that of lipid-based delivery vectors [26]. Recent advances in the development of polymers have regenerated the interest in polymer-mediated gene delivery. Polycationic carriers are either naturally occurring or chemically synthesized compounds. Examples include his-... 

Parekh, H. S., et al. (2006), Synthesis of a library of polycationic lipid core dendrimers and their evaluation in the delivery of an oligonucleotide with hVEGF inhibition, Bioorg. Med. Chem., 14(14), 4775 1780. 

Polymerized lipids do not occur in natural cell membranes. Nature tends to support fragile membrane structures with polymeric skeletons, i.e. protein cytoskeletons, polysaccharide cell walls etc. Analogous synthetic polymeric nets are simply constructed from polymerizable counterions. Negatively charged dihexadecyl phosphate vesicles can be neutralized with choline methacrylate polymerization of the latter produces a polycationic vesicle coat which is not inserted into the membrane (Figure 4.30). A cytoskeleton at the... 

Fasbender A, Zabner J, Chillon M, Moninger TO, Puga AP, Davidson BL, Welsh MJ. Complexes of adenovirus with polycationic polymers and cationic lipids increase the efficiency of gene transfer in vitro and in vivo. J Biol Chem 1997, 272, 6479-6489. 

Beta and co-workers created a total of six polycationic amphiphiles (PA) to study the effect of lipid hydrophobicity on the activity of amphiphilic neomycin B conjugates four of the compounds incorporated either palmitic or arachidic dilipid lysine tails and the other two had single fluorinated undecanoic acid tails. They selected 10 bacteria... 

Regardless of the type of targeting agent, carrier molecules can be subdivided into three classes on the basis of their characteristic length [243] nano-, micro-, and macroscale vectors. In general, nanoscale vectors are represented by polycationic polymers or lipids that self-assemble with NABD to form polyelectrolyte complexes. Microscale vectors usually consist of NABD entrapped within a polymeric matrix, and macroscale vectors are 2D/3D scaffolds or matrices (mainly polymeric but not only) hosting the desired NABD. Of course, it is possible to embed nano-/microscale vectors inside macroscale vectors. Nano-/microscale vectors protect NABD and favor the cellular internalization, while macroscale vectors can modulate nano-/microscale vector release kinetics at the site of action (Figure 15.24). 

Lipid-based carriers, polycationic lipids, polylysine, polyornithine, histones and other chromosomal proteins, hydrogel polymers, all of which can ionically condense DNA and bind to the cell surface are found to be ideal candidates for these vector type. But in the use of different types of cationic liposomes, cationic polymers and dendrimers as non-viral vectors for delivery of genes, it has been observed that in addition to cytotoxicity, these carriers do not lead to satisfactory amount of gene expression in the cells. The reasons are many, particularly, low endosomal escape, no protection of DNA from nuclease... 

With a similar star structure, a kind of polycationic amphiphilic cyclodextrins was reported (Fig. 15b) [118]. The structure contains both cationic elements and lipophilic tails, which is similar to the lipid structure. The nanoparticle stability and transfection efficiency can be rationally modulated by judicious tailoring of the molecular topology. Importantly, by using polycationic amphiphilic CDs that present a dendritic arrangement of catioinic elements in the BNL-CL2 and COS-7... 

Lipid removal may be a critical factor in plaque formation and the location of lecithin-cholesterol trans-acylase in the arterial wall could play an important role since cholesterol is rapidly exchanged" with the blood while cholesterol ester is not. Kuo in an editorial cites the evidence for the theory that a dlsturbemce in carbohydrate metabolism can be responsible for atherosclerosis and should be included as one of the primary risk factors in coronary heart disease. In this regard, Clements and coworkers have shown the presence in aorta of aldose reductase, an enzyme which they feel provides a mechanism for the alteration of arterial metabolism by hyperglycemia. Another approach to molecular interactions was described by Levy and Day who concluded from their results that the low density lipoproteins are uniquely polycationic at the surface and that these ions react with the internal arterial macromolecular polyanions. 

Lipid intermediates have also been implicated in the incorporation of D-galactose into microsomal preparations from beef liver, although they may not be similarly involved in preparations from the mucosal lining of canine trachea. The o-galactosyltransferase activity of the tracheal preparation was subject to control by such polycationic compounds as putrescine, putreanine, cadaverine, protamines, histones, and polylysine at suboptimal concentrations of Mg ions. Galactosyltransferases from rat-liver microsomes exhibited appreciable activity when the nucleotide pyrophosphatase was subjected to control by various uridine nucleotides. ... 

Mecke, A., Majoros, I.J., Patri, A.K., Baker, J.R. r, Banaszak Holl, M.M. and Orr, B.G. (2005) lipid bilayer disruption by polycationic polymers the roles of size and chemical fimctional group. Langmuir, 21,10348-54. 

To date, polycationic moieties have been used for a variety of drugs to enhance their cellular uptake. Most of them are either based on naturally occurring polycationic peptides 83a-c, polycationic peptides such as poly-or oHgo- arginines or lysines 84, 85 or their analogous b-peptides 86, on oligocarbamates 88, on other polycationic peptide scaffolds 87 (Fig. 16) or on polyamine-modified liposomes comprising the polyamine moiety covalently bound to lipids or steroids 41,88,90 as well as on polyamine-modified dendrimers (Fig. 17), as discussed in the next section. 

The insertion of the polymers into monolayers was also studied by comparing the compression isotherms. Lipid monolayers were formed on 0. IM sodium acetate buffer (pH 7.4) subphase in the presence or absence of polymers in a rectangular Teflon cuvette of 28.5 cm x 17.5 cm. After 10 min stabilisation period, a Teflon barrier compressed the monolayer at a speed of 4.2 cm/min and surface pressure vs. area (tc vs. A) isotherms were recorded. Data are summarised in Table 11. We observed no changes in the shape of area vs. pressure curves obtained in the presence of polymers in the subphase (data not shown), but polymers induced an expansion of the monolayer. These changes were detected at various surface pressures (10, 20, 30, 40 and 50 mN/m) and are expressed as area/molecule of phospholipid values (Table 2). These values indicate significant differences in the interaction of polycationic and amphoteric/polyanionic polypeptides. Marked expansion of DPPC monolayer occurred in the presence of SAK or AK (AA=0.23-0.51), while EAK and Ac-EAK initiated only moderate changes in this parameter (AA=0.01-0.13). The effect of polylysine and OAK was negligible (AA=0.01-0.03). 

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