We demonstrate a simple and successful synthetic approach to devise a highly efficient DNA delivery system with low cytotoxicity and low cost. Polyamidoamine (PAMAM) dendrimer is a highly efficient DNA delivery agent, when compared to other chemical transfection reagents. Partially degraded, high-generation dendrimers offer even higher efficiency, presumably due to enhanced flexibility of the otherwise rigid dendrimer chains. We hypothesized that chemical modification of low generation dendrimer with biocompatible poly(ethylene glycol) (PEG) chains would create a conjugate of PAMAM core with flexible PEG chains, which mimics the fractured high-generation dendrimer and produces high transfection efficiency. Generation 5 PAMAM was modified with 3400 molecular weight PEG. The novel conjugate produced a 20-fold increase in transfection efficiency compared with partially degraded dendrimer controls. The cytotoxicity of PEGylated dendrimers was very low. This extremely efficient, highly biocompatible, low-cost DNA delivery system can be readily used in basic research laboratories and may find future clinical applications.

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A new synthetic approach has been applied to obtain novel di-, tetra-, and (multi)-peptide containing polymer conjugates in quantitative yields with a high degree of conjugation. Bis-(N-hydroxysuccinimidyl) esters of PEG (Mw = 200, 600, 1400, 2000, and 3400) were synthesized and studied in a condensation reaction with synthetic peptides: glycine-glycine-tyrosine-arginine (GGYR), a model peptide, and glycine-arginine-glycine-aspartic acid-tyrosine (GRGDY), a sequence known to promote cell adhesion and aggregation. Tetra-substituted derivatives of PEG-based conjugates were synthesized by coupling L-aspartic acid and L-aspartyl-L-phenylalanine through a condensation procedure in organic media. Poly(acrylic acid) and co-polymers (Mw = 2000 and 5000) were studied as a model of multifunctional linear polymers in the reaction with L-tryptophan and GGYR. Alternative polymer-(multi)-peptide conjugates were successfully synthesized using Starburst dendrimer PAMAM (G = 3), 'short' and 'long'-chain PEG-based active esters and GRGDY. The structure of the intermediate precursors and peptide-conjugates was confirmed by spectral (UV-Vis, FTIR, H-NMR) and chromatographic (RP-HPLC and SEC) methods. By varying the properties of the interconnecting polymer--such as hydrophobicity, molecular weight, and functionality--a set of polymer-GRGDY conjugates was synthesized.

These low cost, and adjustable, controlled DNA delivery systems, using FDA-approved biocompatible/biodegradable and implantable/injectable materials, could be useful for in vivo gene delivery, such as DNA vaccination and gene therapy.

Films of PEO and PEO blends were efficiently crosslinked by exposure to ultraviolet radiation with high‐pressure mercury lamp. Photochemical crosslinking proceeded in the presence of photoinitiator such as benzophenone or pentaerythritol triacrylate. PEO networks obtained by UV irradiation in the presence of potassium salts (thiocyanate, perchlorate and triflate) as templates showed enhanced cation binding ability for Li+ and Na+ cations. Cationic networks were prepared from crosslinked PEO modified with ethyl methacrylate dimethyl dodecyl ammonium bromide. Stimuli‐sensitive hydrogels (pH and temperature) were prepared from combinations of PEO and poly‐N‐isopropyl acryl amide, polyvinyl methyl ether, polyvinyl acetate and poly‐2‐vinyl pyridine subjected to UV irradiation.