Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

丙烯酸酯共聚物涂膜中钛螯合物的交联作用

用红外光谱、紫外光谱、差示扫描量热等手段表征了掺杂体系内钛螯舍物(Ti-Ac)与丙烯酸酯共聚物的相互作用。测试了Ti-Ac用量对涂膜耐水性、耐热性及复溶性的影响。鲒果表明。当ωTi-Ac=0．015时涂膜的吸水率可下降到1％以下。且涂膜仍保持较好的复溶性(15s)。     

Gas-to-liquid permeation in silicon-containing, crosslinked, glassy copotymers of methyl methacrylate

Copolymers of methyl methacrylate with disiloxane derivatives have been proposed as biomaterials for contact lens applications. Although glassy, these copolymers exhibit high oxygen permeability and adequate wettability so that they can be used for manufacture of hard, extended wear lenses. CrossHnked copolymers of poly(methyl methacrylate-co-1,3-bis(methacryloxymethyl)-1,1,3,3-tetramethyl-disiloxane), P(MMA-co-BMTDS), containing from 0.085 to 0.53 mole fraction of BMTDS were prepared and tested for oxygen permeation using a novel apparatus which simulates the atmosphere/lens/cornea conditions. The gas-to-liquid dissolved oxygen permeability, P_gd, was determined and it was found to increase with BMTDS content Permeability values for P(MMA-co-BMTDS) at 34°C were significantly higher than for pure homopolymer PMMA, although these copolymers were glassy at this temperature. The increased oxygen permeation was attributed to increased oxygen solubility in the copolymers due to the presence of the -Si-0-bonds.     

Relationship Between Architecture and Adhesion in Polyurethane‐Based Copolymers, 2

Summary: This study describes the chain extension, with polycaprolactone diols, of polyurethane‐graft‐poly(butyl acrylate)s which were first prepared by the step growth polymerization of a mixture of diphenylmethane‐4,4′‐diisocyanate (MDI) and α,α′‐dihydroxyl‐poly(butyl acrylate)s. The success of the chain extension reaction was studied and confirmed by ¹H NMR, SEC and DSC analysis. The incorporation of polycaprolactone sequences in the polyurethane chains modified their specific adhesive properties, bringing cohesion to the material, as demonstrated by tack measurements.

PUR‐graft‐PBA extended with PCL.     

Multidimensional Chromatographic and Hyphenated Techniques for Hydrophilic Copolymers, 1

Summary: The chromatographic analysis of hydrophilic copolymers is complicated due to the fact that in most cases aqueous eluents must be used. In aqueous eluents different polar and ionic effects may disturb the selective interactions between the macromolecules and the stationary phase making it impossible to separate such copolymers with regard to chemical composition. Therefore, 2D chromatography combining a separation according to composition with a separation according to molar mass has been applied mostly to polymers that are soluble in organic solvents. The present contribution describes experimental approaches to analyze such hydrophilic copolymers by 2D‐chromatography. For a model polymer system resulting from the copolymerization of methacrylic acid and a poly(ethylene glycol) macromonomer, it is shown that different analytical techniques including SEC, LC‐CC, MALDI‐TOF MS and 2D chromatography can be used to analyze the different parameters of molecular heterogeneity of such copolymers.

2D separation of poly(MPEG‐MM 2), 1^st dimension: LC‐CC, 2^nd dimension: SEC.     

Molecular and Microdomain Orientation in Semicrystalline Block Copolymer Thin Films by Directional Crystallization of the Solvent and Epitaxy

The directional crystallization of crystallizable organic solvents and the subsequent epitaxial crystallization of crystalline blocks onto the surface of crystalline substrates in semicrystalline block copolymers, control both molecular chain orientation of the crystalline block and the microdomain structure of the block copolymer. Thin film of semicrystalline polystyrene‐block‐poly(ethylene‐alt‐propylene)‐block‐polyethylene (PS/PEP/PE) terpolymer and polystyrene‐block‐polyethylene (PS/PE) diblock copolymer, which both contain crystallizable polyethylene (PE) blocks, have been patterned using benzoic acid (BA) and anthracene (AN) as crystallizable solvents. The directional crystallization induces orientation of the microdomains and epitaxy, due to the crystallographic matching of unit cells between the crystalline PE blocks and the crystalline organic substrates, resulting in the development of highly aligned crystalline PE blocks. The orientation of the PE crystals onto the substrate is evidenced by selected area electron diffraction and bright field transmission electron microscope images. In the case of the PS/PEP/PE terpolymer, the process induces the PS cylinders to align parallel to the b axis of the BA crystals. Long crystalline PE lamellae are oriented edge‐on on the BA surface, with the b axis of PE parallel to the b axis of BA, and parallel to the PS cylinders. In the case of the PS/PE diblock copolymer, the PE cylinders are oriented perpendicular to substrate, packed on a hexagonal lattice. Each cylinder contains precisely one crystalline PE lamella oriented edge‐on on the substrate. When BA is used, the PE lamellae inside cylinders are oriented with the b axis parallel to the b axis of BA crystals. When AN is used, due to the different epitaxial relationship between PE block and AN crystals, the PE lamellae are oriented along two equivalent directions, with the c axis parallel to the [110] and direction of AN crystals.

Schematic model of the final microstructure generated by combination of the directional crystallization and epitaxy.     

Diblock Copolymers Based on 1,4‐Dioxan‐2‐one and ε‐Caprolactone: Characterization and Thermal Properties

Summary: Various poly(ε‐caprolactone‐block‐1,4‐dioxan‐2‐one) (P(CL‐block‐PDX)) block copolymers were prepared according to the living/controlled ring‐opening polymerization (ROP) of 1,4‐dioxan‐2‐one (PDX) as initiated by in situ generated ω‐aluminium alkoxides poly(ε‐caprolactone) (PCL) chains in toluene at 25 °C. 1 ¹H NMR, PCS and TEM measurements have attested for the formation of colloids attributed to a growing PPDX core surrounded by a solvating PCL shell during the polymerization of PDX promoted by ω‐Al alkoxide PCL chains in toluene. The thermal behavior of the P(CL‐block‐PDX) copolymers was studied by DSC; showing two distinct melting temperatures (as well as two glass transition temperatures) similar to those of the respective homopolyesters. Finally, the thermal degradation of the P(CL‐block‐PDX) block copolymers was investigated by TGA simultaneously coupled to a FT‐IR spectrometer and a mass spectrometer for evolved gas analysis (EGA). The degradation occurred in two consecutive steps involving a first unzipping depolymerization of the PPDX blocks followed by the degradation of the PCL blocks via both ester pyrolysis and unzipping reactions.

TEM observation of P(CL‐block‐PDX) block copolyesters ( = 11 600 and = 22 100) as formed by vaporization starting from a diluted suspension in toluene/TCE mixture solvent (50/50 v/v).     

A Novel Macroinitiator for the Synthesis of Triblock Copolymers via Atom Transfer Radical Polymerization: Polystyrene‐block‐poly(bisphenol A carbonate)‐block‐polystyrene and Poly(methyl methacrylate)‐block‐poly(bisphenol A carbonate)‐block‐poly(methyl methacrylate)

Summary: Bis(hydroxy)telechelic bisphenol A polycarbonate (PC) was prepared via melt polycondensation of bisphenol A (BPA) and diphenyl carbonate (DPC) using lanthanum(III ) acetylacetonate as a catalyst for transesterification. Subsequently, the polycarbonate was converted to a bifunctional macroinitiator for atom transfer radical polymerization (ATRP) with the reagent, α‐chlorophenylacetyl chloride. The macroinitiator was used for the polymerization of styrene (S) and methyl methacrylate (MMA) to give PS‐block‐PC‐block‐PS and PMMA‐block‐PC‐block‐PMMA triblock copolymers. These block copolymers were characterized by NMR and GPC. When styrene and methyl methacrylate were used in large excess, significant shifts toward high molecular weights were observed with quantitative consumption of the macroinitiator. Several ligands were studied in combination with CuCl as the ATRP catalyst. Kinetic studies reveal the controlled nature of the polymerization reaction for all the ligands used.

Formation of a bifunctional ATRP macroinitiator by esterification of bis(hydroxy)telechelic PC with α‐chlorophenylacetyl chloride.     

Mixed Hyperbranched/Triblock Copolymer Micelle Assemblies: Physicochemical Properties and Potential for Drug Encapsulation

Mixed micelles have numerous advantages while requiring little to no effort in preparation. This study aims to produce mixed micelle nanostructures from a linear triblock copolymer and a hyperbranched random copolymer, and is able to be loaded with the weakly water-soluble drugs curcumin and indomethacin. Different preparation techniques are employed to produce mixed micelles comprised of Pluronic F127 block copolymer, and hyperbranched poly[(ethylene glycol) methyl ether methacrylate-co-lauryl methacrylate], H-[P(OEGMA-co-LMA)], copolymer. Few studies have dabbled in these types of coassemblies, which provides insight into how structural differences of each copolymer can affect the formation of micelles. To determine the properties of the emerging nanostructures in aqueous environments, including their size, homogeneity, and surface charge, different physicochemical techniques are used, such as light scattering and spectroscopic methods. The results reveal that the copolymers combine, and spontaneously self-assemble into mixed micelle-like nanostructures in aqueous environments, whereas both systems of neat and drug-loaded nanostructures exhibit desirable properties such as small average micelle hydrodynamic radii and low size polydispersity indices. The nanostructures that result from the effective encapsulation of curcumin exhibit outstanding stability over 169 days. The fluorescent qualities of curcumin persist after encapsulation, making the novel nanostructures excellent candidates for bioimaging applications.     

Clonazepam release from core-shell type nanoparticlesin vitro

AB-type amphiphilic copolymers (abbreviated as LE) composed of poly (L-leucine) (PLL) as the A component and poly (ethylene oxide) (PEO) as the B component were synthesized by the ring-opening polymerization of L-leucine N-carboxy-anhydride initiated by methoxy polyoxyethylene amine (Me-PEO-NH₂) and characterized. Core-shell type nanoparticles were prepared by the diafiltration method. Particle size distribution obtained by dynamic light scattering was dependent on PLL composition and the size for LE-1, LE-2 and LE-3 was 369.6±267, 523.4±410 and 561.2±364 nm, respectively. Shapes of the nanoparticles observed by transmission electron microscope (TEM) were almostly spherical. The critical micelle concentration (CMC) of the nanoparticles determined by a fluorescence probe technique was dependent on the composition of hydrophobic PLL, and the CMC for LE-1, LE-2 and LE-3 was 2. 0×10⁻⁶, 1.7×10⁻⁶ and 1.5×10⁻⁶ (mol/l), respectively. Clonazepam release from core-shell type nanoparticles in vitro was dependent on PLL composition and drug loading content.