Wei-Dong He

Shell-cross-linked micelles from PNIPAM-b-(PLL)2 Y-shaped miktoarm star copolymer as drug carriers.

Well-defined AB2 Y-shaped miktoarm star copolymers of PNIPAM-b-(PZLL)2 and PNIPAM-b-(PLL)2 were synthesized through the combination of atom transfer radical polymerization (ATRP), ring-opening polymerization (ROP), and click chemistry, where PNIPAM, PZLL, and PLL are poly(N-isopropylacrylamide), poly(epsilon-benzyloxy-carbonyl-L-lysine), and poly(L-lysine), respectively. Propargyl amine was employed as ROP initiator for the preparation of alkynyl-terminated PZLL. Diazide-terminated PNIPAM was obtained with an azide-containing ATRP initiator. The subsequent click reaction led to the formation of PNIPAM-b-(PZLL)2. After the removal of the benzyloxycarbonyl group, water-soluble PNIPAM-b-(PLL)2 was obtained. The core-shell micelles of PNIPAM-b-(PLL)2 were formed above lower critical solution temperature of PNIPAM block. At this temperature, the shell cross-linking was performed through the reaction between glutaraldehyde and the primary amine groups of the PLL shell, affording the micelles with the endurance to temperature and pH changes. These shell-cross-linked micelles were used as drug nanocarriers and the release profile was dually controlled by the solution temperature and the cross-linking degree.

Formation mechanism of silicone rubber particles with core–shell structure by seeded emulsion polymerization

Silicone rubber particles with core–shell structure were prepared by polymerization of vinyl monomers in the presence of crosslinked and linear poly(dimethyl siloxane-methyl vinyl siloxane) latex. The monomers were added with either continuous or swelled-continuous addition mode. The core–shell morphology of silicone rubber/polystyrene [PST] and silicone rubber/poly(methyl methacrylate-divinyl benzene) [P(MMA-DVB)] composite particles were obtained. The effects of monomer addition mode, the compatibilities of the monomers or their homopolymer with silicone rubber, and the reactivity of polysiloxane with vinyl monomers on the formation of the core–shell structure were discussed.

FORMATION OF MONODISPERSE POLYACRYLAMIDE PARTICLES BY DISPERSION POLYMERIZATION. I. SYNTHESIS AND POLYMERIZATION KINETICS

ABSTRACT Highly monodisperse polyacrylamide (PAM) microparticles were directly prepared by dispersion polymerization in aqueous alcohol media initiated by 2,2′-azobisisobutyronitrile (AIBN) using poly(N-vinylpyrrolidone) (PVP) as a steric stabilizer. Monomer conversion was studied dilatometrically, and polymer molecular weight was determined viscometrically. The gel effect was found evidently from the polymerization kinetics curves. The influences of initiator concentration, monomer concentration, stabilizer content, medium polarity, polymerization temperature on the polymerization rate and the molecular weight of polymer have been examined. The polymerization rate (Rp) can be represented by Rp∝[I]0.52, [M]1.16, [S]0.52, [A/W]0.25 (at A/W value below 1.25), and the molecular weight of polymer can be represented by Mw∝[I]−0.22, [M]1.46, [S]0.25, [A/W]0.19. The overall activation energy for the rate of polymerization is 48.10 kJ/mol (45–55°C). Based on these experimental results, the polymerization mechanisms were discussed primarily.

Formation of long sub-chain hyperbranched poly(methyl methacrylate) based on inhibited self-cyclization of seesaw macromonomers

Well-defined long sub-chain hyperbranched poly(methyl methacrylate) (lsc-hp PMMA) was obtained under reaction conditions that disfavour self-cyclization of the seesaw macromonomer, and its formation was triggered by the intrinsic hindrance of the 1,1-disubstituted chain ends of the seesaw macromonomer. Firstly, seesaw-type alkynyl-(PMMA-Br)2 with one alkynyl group at the chain center and two bromine groups at each chain end was synthesized by atom transfer radical polymerization (ATRP). After the azidation of alkynyl-(PMMA-Br)2, the seesaw macromonomer of alkynyl-(PMMA-N3)2 underwent a click reaction in a high concentration in a good solvent to produce lsc-hp PMMA, almost without intra-chain cyclization of the macromonomer. Compared with our previous reports, the steric hindrance of 1,1-disubstituted MMA units caused almost no self-cyclization of the alkynyl-(PMMA-N3)2 macromonomer. Therefore, lsc-hp PMMA with an exact sub-chain length was obtained except the polydispersity of overall molecular weight. The chemical structure of lsc-hp PMMA was fully confirmed through the combination of gel permeation chromatography (GPC) with different detectors, proton nuclear magnetic resonance spectroscopy and Fourier transform infrared analyses. Furthermore, the formation kinetics for lsc-hp PMMA was monitored based on GPC with a multi-angle laser light scattering detector and followed the equation: ln[(DPw + 1)/2] = [A]0kAB,0(1 − e−αt)/α, where DPw is the absolute weight-average amount of macromonomers in the hyperbranched polymers.

Bactericidal Dendritic Polycation Cloaked with Stealth Material via Lipase-Sensitive Intersegment Acquires Neutral Surface Charge without Losing Membrane-Disruptive Activity

Net cationicity of membrane-disruptive antimicrobials is necessary for their activity but may elicit immune attack when administered intravenously. By cloaking a dendritic polycation (G2) with poly(caprolactone-b-ethylene glycol) (PCL-b-PEG), we obtain a nanoparticle antimicrobial, G2-g-(PCL-b-PEG), which exhibits neutral surface charge but kills >99.9% of inoculated bacterial cells at ≤8 μg/mL. The observed activity may be attributed PCLs responsive degradation by bacterial lipase and the consequent exposure of the membrane-disruptive, bactericidal G2 core. Moreover, G2-g-(PCL-b-PEG) exhibits good colloidal stability in the presence of serum and insignificant hemolytic toxicity even at ≥2048 μg/mL. suggesting good blood compatibility required for intravenous administration.

Comb-Type Grafted Hydrogels of PNIPAM and PDMAEMA with Reversed Network-Graft Architectures from Controlled Radical Polymerizations

Dual thermo- and pH-responsive comb-type grafted hydrogels of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) and poly(N-isopropylacrylamide) (PNIPAM) with reversed network-graft architectures were synthesized by the combination of atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT) polymerization and click chemistry. Two kinds of macro-cross-linkers with two azido groups at one chain-end and different chain length [PNIPAM–(N3)2 and PDMAEMA–(N3)2] were prepared with N,N-di(β-azidoethyl) 2-halocarboxylamide as the ATRP initiator. Through RAFT copolymerization of DMAEMA or NIPAM with propargyl acrylate (ProA) using dibenzyltrithiocarbonate as a chain transfer agent, two network precursors with different content of alkynyl side-groups [P(DMAEMA-co-ProA) and P(NIPAM-co-ProA)] were obtained. The subsequent azido-alkynyl click reaction of macro-cross-linkers and network precursors led to the formation of the network-graft hydrogels. These dual stimulus-sensitive hydrogels exhibited rapid response, high swelling ratio and reproducible swelling/de-swelling cycles under different temperatures and pH values. The influences of cross-linkage density and network-graft architecture on the properties of the hydrogels were investigated. The release of ceftriaxone sodium from these hydrogels showed both thermal- and pH-dependence, suggesting the feasibility of these hydrogels as thermo- and pH-dependent drug release devices.

Efficient and economical synthesis of dendrimer-like polystyrene with long subchains through arm-first divergent strategy

An efficient and economical route for synthesizing well-defined dendrimer-like polymers with long subchains has been developed based on the “arm-first” divergent approach. First, a linear seesaw-type polystyrene (PSt) macromonomer with one alkynyl group at the center and one bromo group at each end was prepared as the constituent unit, and a tri-arm star PSt with three terminal bromo groups as the first generation of dendrimer-like PSt (G1). Then, the second generation of dendrimer-like PSt (G2) carrying six terminal bromo groups was obtained through: (1) the transformation of the terminal bromo group of the former generation (G1) into azido group; (2) alkynyl–azido click reaction between the dendrimer-like polymer and the linear seesaw-type macromonomers; (3) the removal and recovery of excess macromonomers through precipitation in a selective non-solvent. Repeating these steps led to the formation of dendrimer-like PSt up to the fifth generation (G5) with polydispersity index below 1.18. Interestingly, excess PSt macromonomers were separated from the mixture of click reaction by selective precipitation instead of time-consuming fractionation and re-used in the following generation growth, promoting the efficiency and economy of the overall synthesis. The entire generation growth was monitored by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy and gel permeation chromatograph with a multi-angle laser light scattering detector. The thermal and solution properties of dendrimer-like PSts were investigated from the viewpoint of generation number, based on the measurements of glass transition temperature and intrinsic viscosity.

pH-Responsive Self-assembled Nanoparticles of Simulated P(AA-co-SA)-g-PEG for Drug Release

Simulated graft copolymer of poly(acrylic acid-co-stearyl acylate) [P(AA-co-SA)] and poly(ethylene glycol) (PEG) was synthesized, where acrylic acid, stearyl acylate and PEG was employed as the pH-sensitive, hydrophobic and hydrophilic segment, respectively. Polymeric nanoparticles prepared by the dialysis of simulated graft copolymer solution in dimethylformamide against citrate buffer solution with different pH values were characterized by transmission electron microscopy (TEM), fluorescence technique and laser light scattering (LLS). TEM image revealed the spherical shape of the self-aggregates, which was further confirmed by LLS measurements. The critical aggregation concentration increased markedly (10 to 150 mg/L) with increasing pH (4.6 to 7.0), consistent with the de-protonation of carboxylic groups at higher pH. The hydrodynamic radius of polymeric nanoparticles decreased from 118 nm at pH 3.4 to 90 nm at pH 7.0. The controlled release of indomethacin from those nanoparticles was investigated, and the self-assembled nanoparticles exhibited improved performance in controlled drug release.

Influence of crosslinking degree of Silicone rubber particles on properties of epoxy resin

Silicone rubber particles with different degrees of crosslinking were prepared. Silicone oils containing Si—H groups and vinyl groups were reacted at various mol ratios in their composite emulsions. Epoxy resin was modified using these particles and the results indicated that the content of the silicone rubber particles, the crosslinking degree of the rubber particles, and the addition of a coupling agent affected the properties of the modified epoxy resins. The influence of the coupling agent depends on the crosslinking degree of the silicone rubber particles.

Long-subchain Janus-dendritic copolymers from locally confined click reaction and generation-dependent micro-phase separation

In this study, we put forward a divergent synthetic strategy to prepare long-chain Janus-dendritic copolymers with polystyrene (PSt) and poly(tert-butyl acrylate) (PtBA) as each half-dendron. To achieve the exact Janus arrangement, the chemical confinement of half-dendron end-groups and the local confinement of the click reaction were combined. Herein, chemical confinement was satisfied by maintaining one reactant in excess, whereas local confinement was fulfilled through “burying” one reactant. Seesaw macromonomers of PSt and PtBA with one alkynyl group at the chain centre and two bromo groups at the chain ends were used as the constituent units to divergently click onto the related half-dendron. Briefly, the first generation of Janus-dendritic copolymer, J-(PSt)1/(PtBA)1, was synthesized under chemical confinement through click chemistry onto a core molecule with two azido groups. Afterwards, the next two generations of Janus-dendritic copolymers, J-(PSt)2/(PtBA)2 and J-(PSt)3/(PtBA)3, were obtained by click reactions under alternating local and chemical confinement. Fractional precipitation and thin layer chromatography were used to purify the desired products. The variations in chemical composition, end groups, branching units and molecular weight throughout the whole synthesis were monitored with nuclear magnetic resonance spectroscopy, Fourier transfer infrared resonance spectroscopy and gel permeation chromatography. Differential scanning calorimetry, small angle X-ray scattering, atom force microscopy as well as laser light scattering were used to investigate the microphase separation behavior in bulk and the selective solvent. The research results will pave the pathway to polymer synthesis under physical principles and the study of the self-assembly of copolymers with complicated architecture.