Properties of Polyethylenimines

This section will discuss the most important properties of PEIs that are important for its utilization in biomedical applications, namely their solubility and pA a as well as determination of the molar mass. The limitation to PEI is imposed by the fact that this is the only PAI of which sufficiently detailed studies are reported. 

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Table 3.3 Properties of polyethylenimines with covalently-linked aminopyridines.

Meszaros, R. et al.. Adsorption and electrokinetic properties of polyethylenimine on silica surfaces, Langmuir, 18, 6164, 2002. 

An important property of polyethylenimine is its solubility in water in all proportions and the material finds application mostly in the form of aqueous solutions. Typical uses are in the treatment of paper and textiles, for which the cationic polymer has great affinity. 

Li P, Zhang S, Chen S, Zhang Q, Pan J, Ge B (2008) Preparation tmd adsorption properties of polyethylenimine containing fibrous adsorbent for carbon dioxide capture. J Appl Polym Sd 108(6) 3851-3858. doi 10.1002/app.27937... 

Ferrari, S., Pettenazzo, A., Garbati, N., Zacchello, F., Behr, J.P., Scarpa, M. (1999). Polyethylenimine shows properties of interest for cystic fibrosis gene therapy. Bio-... 

Erbacher, P., Bettinger, T., Belguise-Valladier, P., Zou, S., Coll, J.L., Behr, J.P. et al (1999) Transfection and physical properties of various saccharide, poly(ethylene glycol) and antibody-derivatized polyethylenimines (PEI). J. Gene Med., 1,210-222. 

Rao GA, Tsai R, Roura D et al (2008) Evaluation of the transfection property of a peptide ligand for the fibroblast growth factor receptor as part of PEGylated polyethylenimine polyplex. J Drug Target 16 79-89... 

Lin J, Qiu SY, Lewis K et al. (2002) Bactericidal properties of flat surfaces and nanoparticles derivatized with alkylated polyethylenimines. Biotechnol Prog 18 1082-1086... 

More recently, composite membranes have been made by interfacial polymerization or by in situ polymerization A representative case is illustrated in F. 8. Here, a microporous polysulfone membrane is used as a substrate. This membrane is soaked in a dilute aqueous solution of a low molecular weight polyethylenimine (PEI). Without drying, this membrane is then contacted with a crosslinking agent such as toluene diisocyanate (TDI) or isophthaloyl chloride dissolved in hexane, after which the membrane is cured in an oven. A highly crosslinked, salt-rejecting interfacial layer is formed in this way. A summary of the properties of three of the more important composite membranes is presented in Table 10. 

Another approach used for deactivating part of the amine groups of polyethylenimine was to use a partial quaternization of polyethylenimine with ethyl iodide. The membranes formed were similar in properties to those made by the partial polyethylenimine neutralization. Still another type of amine polymer was prepared by free radical polymerization of a mixture of diallylamine hydrochloride, dimethyl diallyl ammonium chloride and sulfur dioxide. This polymer in the free base form for interfacial reaction had reactive secondary amine groups and non-reactive quaternary amine groups ... 

Radeva, T. and Petkanchin, I., Electric properties and conformation of polyethylenimine at the hematite-aqueous solution interface, J. Colloid Intetf. Sci., 196, 87,1997. Ozaki, M., Kratohvil, S., and Matijevic, E., Eormation of monodispersed spindle-type hematite particles, 7. Colloid Interf. Sci., 102, 146, 1984. 

Skachkova AL, Golub TP, Sidorova MP, Omarova KI, Musabekov KB. Elec-trokinetic and adsorption properties of Si02 in OP-7 and polyethylenimine solutions. Colloid J 1991 53 1100-1105. 

Koping-Hoggard et al. [68] established the relationships between the structure and the properties of chitosan-pDNA polyplexes in vitro and in vivo. They compared polyplexes of ultrapure chitosan (UPC) of preferred molecular structure with those of polyethylenimine (PEI) polyplexes in vitro and after intratracheal administration to mice in vivo. UPC carriers were less cytotoxic than polyethylenimine (PEI) polyplexes and provided a better efficiency compared with that of commonly used cationic lipids. Low-molecular weight chitosan delivery systems were more efficient for cell transfection and less cytotoxic compared with PEL [65]. 

Grishina N.V., Rogacheva V.B., Lopatina L.I., Zezin A.B., Kabanov V.A., Transformation of the structure and properties of a complex of poly(acrylic acid) and Unear polyethylenimine during intracomplex amidation in aqueous solutions, Vysokomol. Soedin., SeriyaA, 27(6), 1985, 1154—1159. 

Other chelating polymers related structurally to polyethylenimine and polyethyl-enimine have been derived from cyclopolymerized diallylamines. The structure and properties of these resins have been reviewed by Hodgkin. The attempted synthesis of novel linear poly(lV-alkylethylenimine)s, for metal complexation, by demethylation of ionene polymers has been described.The reaction (involving treatment with UAIH4) was successful only with ionene oligomers. 

Arora and Overberger [215] have studied the optical and photophysical properties of carbazolyl-substituted A/ -acylated polyethylenimines (23 a) and dehydroalanine main-chain polymers (23b). It was established by UV spectroscopy that a local conformational order of the carbazole groups is present in these polymers. Only monomer emission was detected by steady state and... 

It should be noted, however, that the intrinsic properties of a particular chitosan sample depend on structural variables such as the degree of acetylation, the degree of substitution and the average molecular weight. Compared with other amines and polyamines such as polyethylenimine and poly(L-lysine), the primary amino group of the glucosamine unit has an exceptionally low p/Ca value of 6.5, that means that chitosan at pH 7.4 tends to become insoluble because its protonation is low thus, the pH of the transfection medium is important because it affects the transfection efficiency of the chitosan-DNA complexes. In said complexes the N/P ratio (molar ratio of chitosan nitrogen to DNA phosphorous) is also an important parameter. 

The use of modified polyethylenimines was initiated by Klotz et al (21) in binding studies of acylated polyethylenimine with bovine serum albumin and methyl orange. This same group in 1971 applied a similarly modified polyethylenimine containing imidazole groups to the solvolysis of phenyl esters. Because of polyethylenimine s different chemical nature and related solubility properties, polyethylenimine was expected to provide a microenvironment dissimilar to that associated with a vinyl polymer catalyst. The second-order rate constant for the hydrolysis of p-nitrophenylacetate with the modified polyethylenimine, D(10%)-PEI-Im(15%) [10% dodecyl groups,... 

The other possibility is to coat the silica with a polymer of defined properties (molecular weight and distribntion) and olefin groups, e.g., polybutadiene, and cross-linked either by radiation or with a radical starter dissolved in the polymer [32]. This method is preferentially used when other carriers like titania and zirconia have to be surface modified. Polyethylenimine has been cross-linked at the snrface with pentaerythrolglycidether [41] to yield phases for protein and peptide chromatography. Polysiloxanes can be thermally bonded to the silica surface. Other technologies developed in coating fnsed silica capillaries in GC (polysiloxanes with SiH bonds) can also be applied to prepare RP for HPLC. 

The modified polyethylenimines described so far are only a few of many possibilities. It is obvious that this polymer provides a remarkably versatile macromolecular matrix for the attachment of a wide variety of different types of functional groups. Furthermore, the polymer framework makes it possible to juxtapose a binding site, a catalytic group, and an apolar-aqueous interface in a locally compact array. Thus a wide range of local environments can be created on this macromolecular water-soluble catalyst. We hope to be able to exploit these to obtain a series of synthetic macromolecules with tailor-made catalytic properties. 

Abstract Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylenimine and polylysine and their effect on transfection and biocompatibility. Unique scaffolds, such as clusters and polymers based on cyclodextrin (CD), are also discussed, with the focus on recent successes in vivo and in the clinic. These results are presented with the emphasis on the role of carbohydrate and charge on transfection. Use of carbohydrates as molecular recognition ligands for cell-type specific dehvery is also briefly... 

Synthetic polymer. Among the cationic synthetic polymers used for gene delivery are polyethylenimine (PEI), polyamidoamine dendrimers, and poly(2-dimethylaminoethyl methacrylate).161-164 Depending on the flexibility (or rigidity) of the polymers, they form either a small (<100 nm) DNA polyplex or a large (>1 to 10 pm) DNA polyplex.165 More detailed physicochemical properties and their transfection efficacy are to be discussed. 

The last few decades has seen substantial progress in the fabrication of synthetic polymers with biocatalytic properties. A range of polymers has been examined as structural frameworks for the attachment of catalytic groups. For homogeneous catalysts, highly branched polyethylenimines have proved particularly versatile. Modified polystyrenes have served well as foundations for heterogeneous catalysts. 

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