Polyplexes poly -based

A different pH-triggered deshielding concept with hydrophilic polymers is based on reversing noncovalent electrostatic bonds [78, 195, 197]. For example, a pH-responsive sulfonamide/PEl system was developed for tumor-specific pDNA delivery [195]. At pH 7.4, the pH-sensitive diblock copolymer, poly(methacryloyl sulfadimethoxine) (PSD)-hZocA -PEG (PSD-b-PEG), binds to DNA/PEI polyplexes and shields against cell interaction. At pH 6.6 (such as in a hypoxic extracellular tumor environment or in endosomes), PSD-b-PEG becomes uncharged due to sulfonamide protonation and detaches from the nanoparticles, permitting PEI to interact with cells. In this fashion PSD-b-PEG is able to discern the small difference in pH between normal and tumor tissues. 

Physicochemical properties of polyplexes greatly depend on the ratio of poly cation and DNA units in the mixture Z=[polycation units]/[DNA bases] referred to as composition of the mixture (Kabanov and Kabanov, 1995). In the case of polycations containing amino groups, the composition of the mixture is commonly expressed as N/P ratio, i.e., the ratio of the numbers of amino groups of the poly cation to phosphate groups of the DNA. It should be emphasized that the composition of the complex formed after mixing of the polycation and DNA solutions, [Pg.153]

Van de Wetering, P., Schuurmans-Nieuwenbroek, N.M.E., Hennink, W.E. and Storm, G. (1999b) Comparative transfection studies of human ovarian carcinoma cells in vitro, ex vivo and in vivo with poly(2-(dimethylamino) ethyl methacrylate)-based polyplexes. J. Gene Med., 1, 156-165. 

A cyelodextrin-based supramolecular hydrogel system with eationic co-polymer/plasmid DNA (pDNA) polyplexes was studied as a sustained gene delivery carrier. Biodegradable triblock copolymers of metho3gr-poly(ethylene glycol)-Z)-poly(E-caprolactone)-Z)-poly[2-(dimethylamino)ethyl methacrylate]... 

However, being a natural polymer, chitosan has aU disadvantages of natural materials mentioned earlier (see Section 11. A). Presently, a lot of other polyplexes based on cationic synthetic polymers have been described in the literature. Among others, we could mention rather new DNA delivery nanoparticles based on poly(2-dimethylamino)ethyl methacrylate-co-poly(ethylene glycol) (PDMAEMA) [70,71] and PEGylated polyethylenimine (PEI/DNA) [72]. The last polyplexes have been encapsulated in PLGA microparticles and proposed for mucosal (oral) polyplex-based vaccination of Wistar rats. 

Quatemized or partially quatemized derivatives of poly(4-vinylpyridine) (DP = 1,600, Mw = 168 kDa) were synthesized by the group of Izumrudov [210]. Among them, four different series were synthesized quartemized poly(4-vinylpyridine) with V-alkyl ester substituents (C -PVP, Fig. 20b), polycarboxybetaine with alkyl spacer (C -PCB, Fig. 20c), poly[(4-vinylpyridine)-co-(V-alkyl-4-vinylpyridinium)] and poly[(iV-methyl-4-vinylpyridine)-c )-(V-alkyl-4-vinylpyridinium)] both with various alkylation degree p (respectively Cn-PVP-p, Fig. 20d and Me-Cn-PVP-p, Fig. 20e). Unfortunately, relatively few comparisons between these polymers were presented in this publication regarding the physico-chemical characteristics of their polyplexes. At a charge ratio of 5, Cn-PVP-based polyplexes with short V-alkyl... 

Verbaan FJ, Oussoren C, Snel CJ, Crommelin DJA, Hennink WE, Storm G (2004) Steric stabilization of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes mediates prolonged circulation and tumor targeting in mice. J Gene Med 6 64-75... 

In addition to amino-grafted CD polyrotaxane, LPEFyCD-based polypseud-orotaxanes have also been examined for gene delivery [125]. The y-CD-based polypseudorotaxanes had improved cellular uptake and lower toxicity. Unlike the cationic polyrotaxane-based polyplex where DNA was complexed at a lower N/P ratio than that of LPEI, these y-CD-based polypseudorotaxanes required a higher N/P ratio compared to LPEI alone. The transfection efficiency of this poly-pseudorotaxane was comparable to or greater than that of LPEI, especially at higher N/P ratios. 

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