Cationic polymers can self-assemble with DNA to form polyelectrolyte complexes capable of gene delivery, although biocompatibility of the complexes is generally limited. Here we have used A-B type cationic-hydrophilic block co-polymers to introduce a protective surface hydrophilic shielding following oriented self-assembly with DNA. Block co-polymers of poly(ethylene glycol)-poly-L-lysine (pEG-pLL) and poly-N-(2-hydroxypropyl)methacrylamide-poly(trimethylammonioethyl methacrylate chloride) (pHPMA-pTMAEM) both show spontaneous formation of complexes with DNA. Surface charge measured by zeta potential is decreased compared with equivalent polycation-DNA complexes in each case. Atomic force microscopy shows that pHPMA-pTMAEM/DNA complexes are discrete spheres similar to those formed between DNA and simple polycations, whereas pEG-pLL/DNA complexes adopt an extended structure. Biological properties depend on the charge ratio of formation. At optimal charge ratio, pEG-pLL/DNA complexes show efficient transfection of 293 cells in vitro, while pHPMA-pTMAEM/DNA complexes are more inert. Both block co-polymer-DNA complexes show only limited cytotoxicity. Careful selection of block co-polymer structure can influence the physicochemical and biological properties of the complexes and should permit design of materials for specific applications, including targeted delivery of genes in vivo.
Cationic polymer/DNA complexes are widely used for gene delivery, although the influence of the cationic polymer on the biophysical properties of the resulting complex is poorly understood. Here, several series of cationic polymers have been used to evaluate the influence of structural parameters on properties of DNA complexes. Parameters studied included the length of side chain, charge type (primary versus tertiary and quaternary), polymer molecular weight, and charge spacing along the polymer backbone. Cationic polymers with short side chains (such as polyvinylamine) formed small complexes, resistant to destabilization by polyanions, with low surface charge, limited transfection activity, and efficient intranuclear transcription. Conversely, cationic polymers with long side chains (e.g., poly[methacryloyl-Gly-Gly-NH-(CH(2))(6)-NH(2))] showed inefficient complex formation, high positive surface charge, and better transfection activity. The effects of molecular weight varied between polymers, for example, low molecular weight poly(L-lysine) produced relatively small complexes, whereas low molecular weight poly[2-(trimethylammonio)ethyl methacrylate chloride] produced large aggregates. Polymers containing quaternary ammonium groups showed efficient complex formation but poor transfection. Finally, spreading charges widely on the polymer structure inhibited their ability to condense DNA. In summary, to achieve small, stable complexes, the use of cationic polymers with short side chains bearing primary amino groups is suggested.
In this study the methods of synthesis of hydrophilic aldehyde-bearing polymers and copolymers based on 2-deoxy-2-methacrylamido-D-glucose have been developed. Polymers with controllable aldehyde group content were synthesized via free-radical polymerization and subsequent polymeranalogous modification. The water-soluble polymers obtained were investigated in view of their capacity to be adsorbed on two commercial mineral supports used in bone tissue engineering. Besides, cytotoxicity of synthesized polymers was tested.
Abstract:The four first generations of dendrigraft poly-L-lysine have been studied in dimethylformamide (aprotic solvent) and in 0.2 M NaCl aqueous solutions by isothermal translation diffusion, 1 H NMR and viscometry methods. The relationships between diffusion coefficient, intrinsic viscosity and molar mass have been determined for dendrigraft poly-L-lysines, and the scaling index values have been compared to classical trifunctional dendrimers. Dendrimers and dendrigraft poly-L-lysines exhibited similitudes in their hydrodynamic behaviors. Nevertheless, dendrigraft poly-L-lysines displayed a specific behavior in solution. In contrast to dendrimers, a significant change of hydrodynamic dimension of dendrigraft poly-L-lysines according to the nature of the solvent has been observed. In aprotic solvent, the dendrigraft poly-L-lysine dimensions are about two times lower than in aqueous media (i.e., the hydrodynamic volume is contracted by a factor 8 in dimethylformamide), revealing the softness of dendrigraft poly-L-lysine compared to classical trifunctional dendrimers.
OPEN ACCESSPolymers 2012, 4 21
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