Physicochemical evaluation of polymer-DNA complexes for DNA delivery

Available from British Library Document Supply Centre-DSC:DXN052493 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

A versatile synthetic approach to polypeptide based rod-coil block copolymers by click chemistry

Well-defined block copolymers composed of a rigid poly(gamma-benzyl-L-glutamate) (PBLG) sequence and a poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) block were synthesized by Huisgen's 1,3-dipolar cycloaddition (click chemistry) from homopolymers containing azide and alkyne functionalities. These functional groups were introduced in the alpha-position of both PBLG and PDMAEMA precursors using appropriate alpha-omega-functionalized initiators to trigger the living/controlled polymerization of the corresponding monomers. Both alpha-alkyne- and alpha-azido-PBLGs were synthesized by ring-opening polymerization of gamma-benzyl-L-glutamate N-carboxyanhydride at room temperature from amino-containing alpha-alkyne and alpha-azide difunctional initiators, using dimethylformamide as solvent. As for alpha-alkyne-PDMAEMA and alpha-azido-PDMAEMA, they were obtained by copper-mediated atom transfer radical polymerization of 2-(dimethylamino)ethyl methacrylate at 60 degrees C in tetrahydrofuran as solvent. The copper(I)-catalyzed 1,3-dipolar cycloaddition coupling reactions of the alpha-azido-PBLG with the alpha-alkyne-PDMAEMA, in the one hand, and of the alpha-alkyne-PBLG with the alpha-azido-PDMAEMA, on the other hand were conveniently performed in DMF, affording the targeted PBLG-b-PDMAEMA diblock copolymers. Removal of the residual PDMAEMA used in slight excess was facilitated by the retention of this homopolymer onto the stationary phase of the column chromatography. On the basis of size exclusion chromatography, IR and NMR analyses, click chemistry was found to be quantitative, yielding for the first time hybrid diblock copolymers based on a polypeptide and a vinylic polymer

Aggregation behavior and thermodynamics of binding between poly(ethylene oxide)-block-poly(2-(diethylamino)ethyl methacrylate) and plasmid DNA

10.1021/la052591iLangmuir2283744-3750LANG

Well-defined biocompatible block copolymers via atom transfer radical polymerization of 2-methacryloyloxyethyl phosphorylcholine in protic media

2-Methacryloyloxyethyl phosphorylcholine (MPC) is commonly used to prepare biocompatible copolymers that have delivered clinically proven benefits in various biomedical applications. Recently, we reported that MPC could be homopolymerized to high conversions with good control via atom transfer radical polymerization (ATRP) in protic media. In the present study we describe the synthesis of a wide range of well-defined MPC-based block copolymers using either near-monodisperse macroinitiators or sequential monomer addition. With the former approach, the macroinitiators were based on either poly(alkylene oxides) or poly(dimethylsiloxane). With the latter approach, suitable comonomers included a wide range of methacrylic and other monomers, including 2-(dimethylamino)ethyl methacrylate (DMA) and its quaternized derivatives, 2-(diethylamino)ethyl methacrylate (DEA), 2-(diisopropylamino)ethyl methacrylate (DPA), methyl methacrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, and glycerol monomethacrylate. Polymerization of MPC using the three macroinitiators yielded novel PEO−MPC, PPO−MPC, and PDMS−MPC diblock copolymers. The PPO−MPC diblock copolymer proved to be thermoresponsive:  molecular dissolution occurred in cold water, with colloidal aggregates being formed reversibly at elevated temperatures due to the inverse temperature solubility behavior of the PPO block. For the sequential monomer addition syntheses, the MPC monomer was generally polymerized first under optimized conditions, followed by the second monomer. High conversions were obtained for both stages of polymerization, and where applicable, aqueous GPC analyses indicated reasonably low polydispersities and good blocking efficiencies. Above pH 8, the MPC−DMA diblock copolymers also exhibited thermoresponsive behavior, forming DMA-core aggregates at elevated temperature. Spontaneous dissociation occurred on cooling to ambient temperature as the hydrophobic DMA block became hydrophilic again. The MPC−DMA, MPC−DEA, and MPC−DPA diblock copolymers proved to be pH-responsive polymeric surfactants at ambient temperature:  molecular dissolution occurred in dilute acidic solution with well-defined, near-monodisperse micelles being formed at around neutral pH. In each case, the MPC block formed the biocompatible micelle coronas and the tertiary amine methacrylate block formed the hydrophobic micelle cores. In the case of the MPC−DPA diblock copolymer, the pyrene partition constant for the DPA-core micelles at pH 9 was similar to that reported previously for polystyrene-core micelles. These new MPC-based diblock copolymers are being evaluated as new nonviral vectors for DNA condensation and “stealthy” nanocapsules for the delivery of hydrophobic drugs and also for the synthesis of biocompatible shell cross-linked micelles