Novel Nanoparticles Based on Dextran Esters with Unsaturated Moieties

Summary: Applying a dialysis process, new nanoparticles based on well‐defined dextran esters of furan‐2‐carboxylic‐ and pyroglutamic acids were prepared, which can undergo cross‐linking by UV irradiation. The highly functionalized products (total DS > 2) avoid the collapse of nanoparticles due to the prevention of hydrogen bond formation. The major fraction of the dextran ester nanospheres exhibits narrow size distribution down to 250 nm as mean diameter investigated by SEM.

SEM images of dextran furoate pyroglutamate nanospheres.     

Structure design of multifunctional furoate and pyroglutamate esters of dextran by polymer-analogous reactions

Well-defined multifunctionalized dextran esters bearing photo-crosslinkable and chiral groups as well as small alkyl moieties for the adjustment of the solubility were prepared from two dextran samples with different origin and molecular weight. The examination of side structures of the starting dextran was carried out by different one- and two-dimensional NMR techniques. The main synthesis path via in situ activation of furan-2-carboxylic- and pyroglutamic acid with CDI under mild conditions gives highly functionalized dextran derivatives possessing a degree of polymerization in the range of the starting polysaccharide. The subsequent reaction with propionic anhydride leads to completely substituted, CHCl(3) soluble derivatives useful for the determination of the particular degree of substitution. By variation of the molar ratios of polymer to reagent with photo-crosslinkable- and chiral moieties during the reaction and even by subsequent peracylation, multifunctional dextran derivatives with adjustable properties like the hydrophilic/hydrophobic balance were obtained that may form biocompatible spherical nanoparticles.     

Efficient synthesis and characterization of new photoactive dextran esters showing nanosphere formation

Different types of photoactive dextran derivatives with high degree of substitution were prepared by an efficient and mild esterification of the biopolymer with 2-methoxycinnamic acid, [(4-methyl-2-oxo-2H-chromen-7-yl)oxy]acetic acid, and azobenzene-4-carboxylic acid via in situ activation of the carboxylic acid groups with N,N'-carbonyldiimidazole. The structures of the novel dextran esters were evaluated by means of NMR spectroscopy applying the perpropionylated samples. Perpropionylation yields samples soluble in chloroform and acetonitrile that are very useful solvents not only for NMR but also for UV-vis spectroscopic studies. The photochemistry was studied by NMR and UV-vis spectroscopy in the dissolved state and the changes observed may be used to control the properties. The photoactive dextran esters form spherical nanoparticles of a size below 200 nm that are of interest in the design of smart materials.     

Biodegradable nanoparticles made from polylactide-grafted dextran copolymers

Polysaccharide-covered polyester nanoparticles were prepared using the emulsion/solvent evaporation process. The core of the nanoparticles was made either of PLA or of a blend of polylactide and polylactide-grafted dextran copolymer in various proportions. The surface of the nanoparticles was covered by dextran chains via the use of water-soluble polylactide-grafted dextrans as polymeric stabilizers during the emulsification step. The characteristics of the nanoparticles (size, surface coverage, thickness of superficial layer, colloidal stability) were correlated to the structural parameters (length and number of polylactide grafts) of the copolymers as well as to their surface active properties. The complete biodegradability of the nanoparticles was evaluated by considering the rate of hydrolysis of polylactide grafts in phosphate buffer and the rate of enzymatic degradation of dextran backbone by dextranase.     

葡聚糖分子量和接枝度对阿霉素/白蛋白-葡聚糖纳米粒子体外抗肿瘤效果的影响

以Maillard反应制备的牛血清白蛋白-葡聚糖共价接枝物作为载体, 通过调节混合溶液的pH值和温度制备负载阿霉素的白蛋白-葡聚糖纳米粒子. 利用分子量为5×10³, 10×10³和62×10³的葡聚糖制备了多种共价接枝物, 研究了共价接枝物分子量对载药纳米粒子的粒径和稳定性及载药量的影响. 用短链葡聚糖(分子量5×10³和10×10³)制备的纳米粒子粒径为60 nm左右, 用长链葡聚糖(分子量62×10³)制备的纳米粒子粒径约为200 nm; 阿霉素的包埋效率为81%~98%, 包埋量为7.4%~16.9%. 细胞实验结果表明, 共价接枝物具有很好的生物相容性; 与自由阿霉素相比, 纳米粒子可以促进阿霉素进入人口腔上皮癌细胞; 受缓释性质的影响, 纳米粒子在低浓度时的细胞毒性要小于自由阿霉素. 与长链葡聚糖纳米粒子相比, 接枝度高的短链葡聚糖纳米粒子由于具有较小的粒径、 密集的葡聚糖分子刷表面、 一定的自由阿霉素浓度和较快的阿霉素释放速率, 因而更容易进入细胞并具有更好的体外抗肿瘤活性.     

Evaluation of the surface properties of dextran-coated poly(isobutylcyanoacrylate) nanoparticles by spin-labelling coupled with electron resonance spectroscopy

Poly(alkylcyanoacrylate) nanoparticles are developed as carrier for the in vivo delivery of drugs. In this area of research, one of the major challenges is to design nanoparticles able to carry a drug to a specific site in the body. This appears to be mainly governed by the surface properties of the carrier. Results from previous independent studies suggest that the way dextran chains are arranged at the nanoparticle surface can affect the in vivo fate of the carrier. Thus, the purpose of the present study was to investigate for the first time whether electronic paramagnetic resonance (EPR) could highlight a difference between the physico-chemical surface properties of dextran-coated nanoparticles obtained by two different emulsion polymerisation mechanisms of isobutylcyanoacrylate. Poly(isobutylcyanoacrylate) nanoparticles were prepared either by anionic or by radical polymerisation, initiated in both cases by dextran. The respective copolymers self-organised as nanoparticles. Dextran chains located at the nanoparticle surface could be labelled with a free nitroxide radical containing a probe and EPR analysis could be performed on freeze-dried nanoparticles, rehydrated nanoparticles and dispersed nanoparticles in water. The mobility of dextran chains appeared to differ according to the degree of hydration of the systems. More interestingly, EPR spectra clearly highlighted differences in dextran chain mobility comparing the nanoparticles obtained by radical and anionic polymerisation. Therefore, this technique opens an interesting prospect of investigating surface properties of polysaccharide-coated nanoparticles by a new physico-chemical approach to further correlate the mobility of the polysaccharide chains with the fate of the nanoparticles in biological systems.     

Quadruple‐Responsive Nanocomposite Based on Dextran–PMAA–PNIPAM,Iron Oxide Nanoparticles,and Gold Nanorods

A quadruple‐responsive nanocomposite that responds to temperature, pH, magnetic field, and NIR is obtained by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) and gold nanorods (AuNRs) into a dextran‐based smart copolymer network. The dual‐sensitive copolymer is prepared by sequential RAFT polymerization of methacrylic acid and N‐isopropylacrylamide from trithiocarbonate groups linked to dextran in one pot. These functionalized nanocomposites with superior stability can respond to the four stimuli mentioned above well. As evidenced by UV–vis and TEM measurements, the temperature‐induced unusual blue‐shift in the longitudinal plasmon band is possibly due to the side‐to‐side assembly of AuNRs.     

Preparation of dextran immunological magnetic nanoparticles and their application to combined targeting carrier

Superparamagnetic dextran nanoparticles were prepared by coprecipitation. Effects of concentration of dextran, amount of ironic salts, stirring speed, concentration of ammonium hydroxide and mole ratio of Fe3+/Fe2+ on the effective diameter of dextran magnetic nanopartides (DMNP) were studied. Dextran immunological magnetic nanoparticles (DIMNP) were formed by the reaction of the monoclonal anti-human mammary cancer antibody with DMNP oxidized by sodium periodate, and the properties of magnetic susceptibility, shape and retention of antibody activity were investigated. The in vitro cancer antigen binding ability of DIMNP was demonstrated by radioimmunoassay, and the in vivo magnetic localization and antibody targeting ability of radiolabeled DIMNP were studied.     

Nanoparticles of hydrophobically modified dextrans as potential drug carrier systems

Nanoparticles combining a hydrophobically modified dextran core and a polysaccharide surface coverage were elaborated. Their suitability for applications like drug delivery was evaluated. The selected polysaccharide, dextran, was chemically modified by the covalent attachment of hydrocarbon groups (aliphatic or aromatic) via the formation of ether links. According to the extent of modification, either water-soluble or water-insoluble dextran derivatives were obtained. The latter exhibited solubility in organic solvents like tetrahydrofuran or dichloromethane saturated with water. Water-soluble dextran derivatives were used as polymeric surfactants for the control of nanoparticles surface characteristics. Nanoparticles were prepared either by o/w emulsion or solvent-diffusion methods. The size and surface properties of dextran nanoparticles were correlated to processing conditions. The stability of colloidal suspensions was examined as a function of ionic strength and related to the particle surface characteristics. The redispersability of freeze-dried suspensions without the addition of cryoprotectant was demonstrated. Finally, the degradability of modified dextrans was compared to that of starting dextran, after enzymatic hydrolysis in the presence of dextranase.     

A facile one-pot method to fabricate gold nanoparticle chains with dextran

A biocompatible water-soluble dextran has been used for controllable one-dimensional assembly of gold nanoparticles via a one-pot method.Long gold nanoparticle chains with good dispersion in water could be easily obtained after adding dextran into the mixture of HAuCl 4 and sodium citrate.The measurements of scanning electron microscopy(SEM) and dynamic light scattering(DLS) confirmed the formation of gold nanoparticle chains.The morphology and dispersion properties of gold nanoparticle chains could be tuned by adjustment of the reagent ratio,stirring speed,and reaction time.     

Preparation and characterization of polyaniline microwires containing CdS nanoparticles

Polyaniline(PANI) microwires containing CdS nanoparticles have been prepared by introducing hydrogen bonding and/or electrostatic interaction between mercaptocarboxylic acid capped CdS nanoparticles and PANI. SEM and TEM proved them to be wire-like structures. PL spectra of the PANI/CdS complex is blue-shifted by 14 nm compared to CdS nanoparticles in N-methylpyrrolidinone(NMP).     

Synthesis and characterization of positively charged,alumina‐coated silica/polystyrene hybrid nanoparticles via pickering miniemulsion polymerization

Positively charged, raspberry‐like hybrid nanoparticles, consisting of a polystyrene core and an alumina‐coated silica shell were successfully prepared in a surfactant free system via the radical copolymerization of styrene (St) and different comonomers (acrylic acid, methacrylic acid, and acrylamide) by using a cationic silica sol as the sole emulsifier in Pickering miniemulsion polymerization. The influence of different parameters like pH of the dispersion, comonomer content, and the amount and size of silica nanoparticles on the colloidal stability of the systems, prepared with different comonomers, was examined. The particles' morphology was observed via high‐resolution scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The removal of free silica particles via centrifugation was proved by TEM and SEM, and the content of free and adsorbed silica was quantified via thermogravimetric analysis (TGA). © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

纳米ZnO对白僵菌孢子的紫外保护及与孢子的生物相容性

用沉淀法制备经油酸表面修饰的纳米ZnO,测定其紫外吸收性能及对油悬浮剂型白僵菌孢子的抗紫外保护效率;用扫描电子显微镜观察纳米ZnO与孢子的混合状态,通过对含纳米ZnO的白僵菌制剂在贮存期间孢子萌发率差异显著性的分析,确定其与白僵菌孢子的生物相容性.结果表明：制备的纳米ZnO的平均粒径为27nm,其对波长200nm～370nm范围的紫外光具有良好的吸收性能.含纳米ZnO质量分数为1.0%、2.0%和5.0%的油悬浮剂型白僵菌,紫外灯照射8h,对孢子保护效率均大于60%,不含纳米ZnO为9.7％. 纳米ZnO被吸附包覆于孢子表面,屏蔽紫外线,保护孢子免受紫外线的杀伤.含0.5%、1.0%和2.0%纳米ZnO的油悬浮剂型白僵菌制剂室温贮存10个月,其孢子萌发率与不含纳米ZnO的差异不显著;纳米ZnO与白僵菌孢子生物相容性好.油悬浮剂型白僵菌制剂中纳米ZnO的适宜含量为1.0%～2.0%.     

Identification of acidic phosphorus-containing ligands involved in the surface chemistry of CdSe nanoparticles prepared in tri-N-octylphosphine oxide solvents

The surface ligand composition of CdSe nanoparticles prepared using technical grade tri-n-octylphosphine oxide (TOPO) was investigated using a nucleophilic ligand displacement methodology and (31)P {(1)H} NMR spectroscopy. 4-(N,N-Dimethylamino)pyridine (DMAP) and benzyltrimethylammonium propionate were added to tetrahydrofuran solutions of CdSe nanoparticles prepared in technical grade TOPO. DMAP was shown to be a sufficiently strong nucleophile to displace the more weakly coordinating ligands, TOPO, TOPSe, di-n-octylphosphinate, and n-octylphosphonate (OPA). Benzyltrimethylammonium propionate was shown to be a stronger nucleophile than DMAP in that it could displace all the aforementioned surface-bound ligands as well as a previously unidentified surface-bound phosphorus species. Independent synthesis and (31)P {(1)H} NMR spectral matching confirmed that the new species was P,P'-(di-n-octyl) dihydrogen pyrophosphonic acid (PPA). The PPA was shown to form during the nanoparticle synthesis via the dehydrative condensation of OPA. CdSe nanoparticle syntheses were performed using pure TOPO and added OPA, and subsequent displacement experiments showed that OPA and PPA were the predominant surface-bound ligands. CdSe nanoparticle syntheses were performed using pure TOPO and added PPA, and subsequent displacement experiments showed that PPA was the predominant surface-bound ligand. PPA was also shown to have the greatest affinity for the nanoparticle surface of all the ligands investigated. Thus, a model for the surface ligand composition could be developed for nanoparticles prepared using technical grade TOPO or other high-boiling solvents with added acidic phosphorus compounds.     

Unstirred preparation of soluble electroconductive polypyrrole nanoparticles

Soluble electro-conductive polypyrrole nanoparticles (PPY-NPs) doped with organic sulfonic acid can be easily prepared via a new method for unstirred polymerization. The yield, size, morphology, electrical conductivity and solubility of the PPY-NPs were optimized by changing the feeding oxidant method, the sulfonic acid, the oxidant, and steric stabilizers. The PPY-NPs were characterized by FTIR, wide angle X-ray diffraction and four-point probe techniques. The morphology of the nanoparticles was investigated using scanning electron microscopy (SEM) and transmission electron microscopy. The PPY-NPs doped with p-toluenesulfonic acid exhibit a small diameter, an electrical bulk conductivity of 52.7 S·cm^?1, and can be obtained in high yield. PPY-NPs doped with naphthalene-2-sulfonic acid have a minimum mean diameter of around 71 nm (as found by SEM). All doped PPY-NPs are well solube in dimethylformamide, dimethyl sulfoxide, formic acid and sulfuric acid.     

Bioartificial materials based on blends of dextran and poly(vinyl alcohol-co-acrylic acid)

Bioartificial polymeric materials based on blends of dextran and poly(vinyl alcohol-co-acrylic acid) P(VA-co-AA) were prepared in the form of films and characterised to evaluate the miscibility of the natural component with the synthetic one. The idea of this work was to compatibilise PVA and dextran by introducing carboxylic groups along the PVA chains.The copolymer was synthesised and characterised in our laboratories. The results evidenced that the copolymer had an appropriate molecular weight and the content of PAA in the copolymer was 45% (weight). Then, films with different composition ratios were prepared by solution casting and analysed by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), chemical imaging analysis and mechanical tests. The results obtained indicated that the introduction of carboxylic groups along the PVA chains had a positive effect on the miscibility degree of the synthetic component with the biological one.     

Electrochemical Sensor for Oxidation of NO Based on Au-Pt Nanoparticles Self-assembly Film

Au-Pt bimetallic nanoparticles film used as an efficient electrochemical sensor was prepared by self-assembled Au-Pt bimetallic nanoparticles on a glassy carbon (GC) substrate using thioglycolic acid as a linker. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) showed that the Au-Pt nanoparticles self-assembly film was dense and uniform. Electrochemical experiments revealed that Au-Pt bimetallic nanoparticles film/GC electrode showed high electrocatalytic activity to the oxidation of nitric oxide.     

2-nitrophenyl isocyanide as a versatile convertible isocyanide: rapid access to a fused gamma-lactam beta-lactone bicycle

2-Nitrophenyl isocyanide is introduced as a convertible isocyanide with demonstration of its feasibility and applicability in an efficient synthesis of the fused gamma-lactam beta-lactone bicycle of proteasome inhibitor omuralide. Starting from a linear keto acid precursor, the fused gamma-lactam beta-lactone bicycle was prepared in four steps by a sequential biscyclization strategy; a stereocontrolled Ugi reaction and the concomitant direct beta-lactonization following the formation of an N-acylbenzotriazole intermediate. The N-acylbenzotriazole is amenable to intra- or intermolecular attack from a variety of nucleophiles with a catalytic amount of base to form the pyroglutamic acid derivatives.     

In vitro enzymatic degradation of nanoparticles prepared from hydrophobically-modified poly(gamma-glutamic acid)

Amphiphilic poly(gamma-glutamic acid) (gamma-PGA) was prepared by the introduction of L-phenylalanine ethylester (L-PAE) as a side chain. This gamma-PGA-graft-L-PAE formed monodispersed nanoparticles in water. The particle size of the gamma-PGA nanoparticles could be controlled by the degree of L-PAE grafting. The hydrolytic degradation and enzymatic degradation by gamma-glutamyl transpeptidase (gamma-GTP) of these gamma-PGA nanoparticles was studied by gel permeation chromatography (GPC) and scanning electron microscopy (SEM). The hydrolysis ratio of gamma-PGA was found to decrease upon increasing the hydrophilicity of the gamma-PGA. The degradation of the gamma-PGA backbone by gamma-GTP resulted in a dramatic change in nanoparticle morphology. With increasing time, the gamma-PGA nanoparticles reduced in size and finally disappeared completely.Time-course of the changes in the morphology of the gamma-PGA nanoparticles following incubation with gamma-glutamyl transpeptidase.     

Preparation of cyanoacrylate nanoparticles using monosaccharides or disaccharides

By using biomaterials, including monosaccharides and disaccharides, as polymeric stabilizing agents, the cyanoacrylate nanoparticles was prepared respectively, with particles diameter of approximately 200 nm or 300 nm. The new method was applied to load/encapsulate ampicillin (ABPC) and pDNA into nanoparticles. Loading efficiency of ABPC was increased compared to the existing method in which dextran is used as a stabilizer. The pDNA encapusulation rate was 68.7%, by using glucose.