Hydrophilization of Magnetic Nanoparticles with Modified Alternating Copolymers. Part 1: The Influence of the Grafting

Iron oxide nanoparticles (NPs) with a diameter 21.6 nm were coated with poly(maleic acid-alt-1-octadecene) (PMAcOD) modified with grafted 5,000 Da poly(ethyelene glycol) (PEG) or short ethylene glycol (EG) tails. The coating procedure utilizes hydrophobic interactions of octadecene and oleic acid tails, while the hydrolysis of maleic anhydride moieties as well as the presence of hydrophilic PEG (EG) tails allows the NP hydrophilicity. The success of the NP coating was found to be independent of the degree of grafting which was varied between 20 and 80% of the -MacOD-units, but depended on the length of the grafted tail. The NP coating and hydrophilization did not occur when the modified copolymer contained 750 Da PEG tails independently of the grafting degree. To explain this phenomenon the micellization of the modified PMAcOD copolymers in water was analyzed by small angle x-ray scattering (SAXS). The PMAcOD molecules with the grafted 750 Da PEG tails form compact non-interacting disk-like micelles, whose stability apparently allows for no interactions with the NP hydrophobic shells. The PMAcOD containing the 5,000 Da PEG and EG tails form much larger aggregates capable of an efficient coating of the NPs. The coated NPs were characterized using transmission electron microscopy, dynamic light scattering, ζ-potential measurements, and thermal gravimetry analysis. The latter method demonstrated that the presence of long PEG tails in modified PMAcOD allows the attachment of fewer macromolecules (by a factor of ~20) compared to the case of non-modified or EG modified PMAcOD, emphasizing the importance of PEG tails in NP hydrophilization. The NPs coated with PMAcOD modified with 60% (towards all -MAcOD- units) of the 5,000 PEG tails bear a significant negative charge and display good stability in buffers. Such NPs can be useful as magnetic cores for virus-like particle formation.     

Nanoparticle Capping Agent Controlled Electron‐Transfer Dynamics in Ionic Liquids

Herein, we report a change in the mechanism of the oxidation of silver nanoparticles (Ag NPs) with the molecular weight of a poly(ethylene) glycol (PEG) capping agent. Characterisation of the modified nanoparticles is undertaken using dynamic light scattering and UV/Vis spectroscopy. Electrochemical analyses reveal that the oxidation of 6000 molecular weight (MW) PEG is consistent with a polymer‐gated mechanism, whilst for 2000 MW PEG the polymer does not hinder the oxidation. The 10,000 MW PEG Ag NPs are rendered almost electrochemically inactive. This study demonstrates the ability to alter and better understand the electron‐transfer mechanism in a room temperature ionic liquid (RTIL) by systematically altering the capping agent.     

双分布聚乙二醇接枝纳米二氧化硅的高效可控制备

在混合溶剂中通过"grafting to"的方法将2种分子量不同的聚乙二醇单甲醚(MPEG M_w=750,4000)接枝到氨基修饰的St?ber法二氧化硅(SiO_2-NH_2)表面,制备双分布纳米接枝复合物.采用二步法,先将带环氧端基的低分子量聚乙二醇单甲醚(MPEG-EO)与SiO_2-NH_2在甲苯溶剂中充分反应后,与高分子量的MPEG-EO在甲苯和正癸烷的混合溶剂中使用相同的反应条件和后处理方法,能便捷制备出具有双分布接枝的纳米复合物.在接枝反应体系中,分子链的链段尺寸和接枝密度之间存在着密切关系.一定的范围内,接枝密度随链段尺寸减小而增大.通过改变混合溶剂比例来调控接枝链段的尺寸,可以很好控制聚合物的接枝密度.在双分布接枝的纳米复合物中,低分子量的接枝密度为0.85 chains/nm~2,高分子量的接枝密度能达到0.40 chains/nm~2,体现出了简单、高效、可控的特点,与聚环氧乙烷(PEO)共混后分散良好,对于制备出均匀分散的纳米复合材料起到了一定的指导作用.     

Microporous structure and drug release kinetics of polymeric nanoparticles

The aim of the present study was to characterize pegylated nanoparticles (NPs) for their microporosity and study the effect of microporosity on drug release kinetics. Blank and drug-loaded NPs were prepared from three different pegylated polymers, namely, poly(ethylene glycol)1%-graft-poly(D,L)-lactide, poly(ethylene glycol)5%-graft-poly(D,L)-lactide, and the multiblock copolymer (poly(D,L)-lactide-block-poly(ethylene glycol)-block-poly(D,L)-lactide)n. These NPs were characterized for their microporosity using nitrogen adsorption isotherms. NPs of the multiblock copolymer showed the least microporosity and Brunauer-Emmett-Teller (BET) surface area, and that of PEG1%-g-PLA showed the maximum. Based on these results, the structural organization of poly(D,L)-lactide (PLA) and poly(ethylene glycol) (PEG) chains inside the NPs was proposed and was validated with differential scanning calorimetry (DSC) and X-ray photoelectron spectroscopy (XPS) surface analysis. An in vitro drug release study revealed that PEG1%-g-PLA NPs exhibited slower release despite their higher surface area and microporosity. This was attributed to the presence of increased microporosity forming tortuous internal structures, thereby hindering drug diffusion from the matrix. Thus, it was concluded that the microporous structure of NPs, which is affected by the molecular architecture of polymers, determines the release rate of the encapsulated drug.     

Surfactant--polymer aggregates formed by sodium dodecyl sulfate, poly(N-vinyl-2-pyrrolidone), and poly(ethylene glycol)

The interaction of sodium dodecyl sulfate (SDS) in aqueous solution with poly(N-vinyl-2-pyrrolidone) (M(w) = 55,000 g/mol) in the presence of poly(ethylene glycol) (M(w) = 8000 g/mol) is investigated by electrical conductivity, zeta potential measurements, viscosity measurements, fluorescence spectroscopy, and small-angle X-ray scattering (SAXS). The results indicate that SDS-polymer interaction occurs at low surfactant concentration, and its critical aggregation concentration is fairly dependent on polymer composition. The polymer-supported micelles have average aggregation numbers dependent on surfactant concentration, are highly dissociated when compared with aqueous SDS micelles, and have zeta potentials that increase linearly with the fraction of PVP at constant SDS concentration. The analysis of the SAXS measurements indicated that the PVP/PEG/SDS system forms surface-charged aggregates of a cylindrical shape with an anisometry (length to cross-section dimension ratio) of about 3.0.     

In vitro macrophage uptake and in vivo biodistribution of long-circulation nanoparticles with poly(ethylene-glycol)-modified PLA (BAB type) triblock copolymer

The effect of the PEG-grafted degree in the range of 0–30% on the in vitro macrophage uptake and in vivo biodistribution of poly(ethylene glycol)–poly(lactic acid)–poly(ethylene glycol) (PELE) nanoparticles (NPs) were investigated in this paper. The prepared NPs were characterized in terms of size, zeta potential, hydrophilicity, poly(vinyl alcohol) (PVA) residual on nanoparticles surfaces as well as drug loading. The macrophage uptake and biodistribution including plasma clearance kinetics following intravenous administration in mice of the NPs labeled by 6-coumarin were evaluated. The results showed that, except for the particles size, the hydrophilicity, superficial charges and in vitro phagocytosis amount of NPs are dependent on the PEG content in the copolymers greatly. The higher of the PEG content, the more hydrophilicity and the nearer to neutral surface charge was observed. And the prolonged circulation half-life (t_1/2) of the PELE NPs in plasma was also strongly depended on the PEG content with the similar trend. In particular for PELE30 (containing 30% of PEG content) NPs, with the lowest phagocytosis uptake accompanied the highest hydrophilicity and approximately neutral charge, it had the longest half-life in vivo with almost 12-fold longer and accumulation in the reticuloendothelial system organs close to 1/2-fold lower than those of reference PLA. These results demonstrated that the PELE30 NPs with neutral charge and suitable size has a promising potential as a long-circulating oxygen carrier system with desirable biocompatibility and biofunctionality.     

SANS studies of the effects of surfactant head group on aggregation properties in water/glycol and pure glycol systems

Aggregation in mixed water-glycol and pure glycol solvents has been investigated with four related surfactants, bearing common C12 tails: anionic, sodium dodecylsulfate (SDS); cationic, dodecyltrimethylammonium bromide (C12TAB); zwitterionic C12-amidopropyldimethylamine betaine (betaine) and nonionic, octaethyleneglycol monododecyl ether (C12E8). The solvent media were water, water/ethylene glycol, and water/propylene glycol mixtures, as well as pure ethylene glycol (EG) and propylene glycol (PG), spanning relative dielectrics epsilon(r) from 79 to 30. Results from small-angle neutron scattering (SANS) experiments, employing deuterated solvents, were consistent with the presence of ellipsoidal, or cylindrical micelles, depending on solvent and surfactant type. In pure EG and PG solvents the ionic and zwitterionic surfactants exhibit only weak aggregation, with much smaller micelles than normally found in water. However, interestingly, pure EG is identified as a solvent in which nonionic C12E8 aggregates strongly, mirroring the behavior in water. In contrast when the solvent is changed to PG (epsilonr=30) aggregation of C12E8 is only minimal. Hence, aggregation is shown to be strongly dependent on surfactant type and identity of the glycol solvent.     

Mixed Co/Fe oxide nanoparticles in block copolymer micelles

Small iron oxide and Co-doped iron oxide nanoparticles (NPs) were synthesized in a commercial amphiphilic block copolymer, poly(ethylene oxide)-b-poly(methacrylic acid) (PEO 68-b-PMAA8), in aqueous solutions. The structure and composition of the micelles containing guest molecules (metal salts) or NPs (metal oxides) were studied using transmission electron microscopy, dynamic light scattering, X-ray photoelectron spectroscopy, and X-ray powder diffraction. The enlarged micelle cores after incorporation of metal salts are believed to be formed by both PMAA blocks containing metal species and penetrating PEO chains. The nanoparticle size distributions in PEO 68-b-PMAA8 were determined using small-angle X-ray scattering (SAXS) in bulk. Two independent methods for SAXS data interpretation for comprehensive analysis of volume distributions of metal oxide NPs showed presence of both small particles and larger entities containing metal species which are ascribed to organization of block copolymer micelles in bulk. The magnetometry measurements revealed that the NPs are superparamagnetic and their characteristics depend on the method of the NP synthesis. The important advantage of the PEO 68-b-PMAA8 stabilized magnetic nanoparticles described in this paper is their remarkable solubility and stability in water and buffers.     

Multilayers and poly(allylamine hydrochloride)-graft-poly(ethylene glycol) modified bovine serum albumin nanoparticles: Improved stability and pH-responsive drug delivery

To improve the colloidal stability of bovine serum albumin(BSA) nanoparticles(NPs) in diverse mediums, poly(allylamine hydrochloride)(PAH)/sodium poly(4-styrene sulfonate)(PSS) multilayers and poly(allylamine hydrochloride)-graft-poly(ethylene glycol)(PAH-g-PEG) coating were coated on the surface of BSA NPs.Stabilities of the BSA NPs in diverse mediums with different surfaces were detected by dynamic light scattering(DLS).Multilayers and PAH-g-PEG coated BSA NPs can be well dispersed in various mediums with a narrow polydispersity index(PDI).The BSA NPs with the highest surface density of PEG show the best stability.The multilayers and PAH-g-PEG coating do not deter the pH-dependent loading and release property of BSA NPs.At pH 9,the encapsulation efficiency of doxorubicin reaches almost 99%,and the release rate at pH 5.5 is significantly higher than that at pH 7.4.     

Encapsulation of silica nanoparticles by redox-initiated graft polymerization from the surface of silica nanoparticles

This study describes a facile and versatile method for preparing polymer-encapsulated silica particles by ‘grafting from’ polymerization initiated by a redox system comprising ceric ion (Ce⁴⁺) as an oxidant and an organic reductant immobilized on the surface of silica nanoparticles. The silica nanoparticles were firstly modified by 3-aminopropyltriethoxysilane, then reacted with poly(ethylene glycol) acrylate through the Michael addition reaction, so that hydroxyl-terminated poly(ethylene glycol) (PEG) were covalently attached onto the nanoparticle surface and worked as the reductant. Poly(methyl methacrylate) (PMMA), a common hydrophobic polymer, and poly(N-isopropylacrylamide) (PNIPAAm), a thermosensitive polymer, were successfully grafted onto the surface of silica nanoparticles by ‘grafting from’ polymerization initiated by the redox reaction of Ce⁴⁺ with PEG on the silica surface in acid aqueous solutions. The polymer-encapsulated silica nanoparticles (referred to as silica@PMMA and silica@PNIPAAm, respectively) were characterized by infrared spectroscopy, thermogravimetric analysis, and transmission electron microscopy. On the contrary, graft polymerization did not occur on bare silica nanoparticles. In addition, during polymerization, sediments were observed for PMMA and for PNIPAAm at a polymerization temperature above its low critical solution temperature (LCST). But the silica@PNIPAAm particles obtained at a polymerization temperature below the LCST can suspend stably in water throughout the polymerization process.     

Enhanced crystallization behaviors of poly(ethylene terephthalate) via adding expanded graphite and poly(ethylene glycol)

A compound additive system consisting of expanded graphite (EG) and poly(ethylene glycol) (PEG) was designed to enhance the crystallization of poly(ethylene terephthalate) (PET). In this additive system, EG acted as a heterogeneous nucleating agent to reduce energy barrier for nucleation, while PEG played as plasticizer to improve mobility of PET chains. Simultaneously adding EG and PEG resulted in faster crystallization kinetics than the cases of solely adding EG or PEG in both of non-isothermal and isothermal crystallization processes, indicating a synergistic effect of EG and PEG on enhancing PET crystallization. However, for non-isothermal crystallization process, in which crystallization occurred from a cooling melt, EG played a dominant role. As to isothermal crystallization process where crystallization took place in a super-cooling state, PEG seemed to be more important. Moreover, the chain conformation change among the semi-crystalline PET specimens was ascertained by Fourier transform infrared spectroscopy.     

Synthesis of poly(ethylene glycol) (PEG)-grafted colloidal silica particles with improved stability in aqueous solvents

The known grafting procedures of colloidal silica particles with poly(ethylene glycol) (PEG) lead to grafting layers that detach from the silica surface and dissolve in water within a few days. We present a new grafting procedure of PEG onto silica with a significant improvement of the stability of the grafting layers in aqueous solvents. Moreover, the procedure avoids any dry states or other circumstances leading to strong aggregation of the particles. To achieve the improved water stability, St?ber silica particles are first pre-coated with a silane coupling agent (3-aminopropyl)triethoxysilane (APS) to incorporate active amine groups. The water solubility of the pre-coating layer was minimized using a combination of APS with bis-(trimethoxysilylpropyl)amine (BTMOSPA) or bis-(triethoxysilyl)ethane (BTEOSE). These pre-coated particles were then reacted with N-succinimidyl ester of mono-methoxy poly(ethylene glycol) carboxylic acid to form PEG-grafted silica particles. The particles form stable dispersions in aqueous solutions as well as several organic solvents.     

Target‐Specific Capture of Environmentally Relevant Gaseous Aldehydes and Carboxylic Acids with Functional Nanoparticles

Aldehyde and carboxylic acid volatile organic compounds (VOCs) present significant environmental concern due to their prevalence in the atmosphere. We developed biodegradable functional nanoparticles comprised of poly(d,l ‐lactic acid)‐poly(ethylene glycol)‐poly(ethyleneimine) (PDLLA‐PEG‐PEI) block co‐polymers that capture these VOCs by chemical reaction. Polymeric nanoparticles (NPs) preparation involved nanoprecipitation and surface functionalization with branched PEI. The PDLLA‐PEG‐PEI NPs were characterized by using TGA, IR, ¹H NMR, elemental analysis, and TEM. The materials feature 1°, 2°, and 3° amines on their surface, capable of capturing aldehydes and carboxylic acids from gaseous mixtures. Aldehydes were captured by a condensation reaction forming imines, whereas carboxylic acids were captured by acid/base reaction. These materials reacted selectively with target contaminants obviating off‐target binding when challenged by other VOCs with orthogonal reactivity. The NPs outperformed conventional activated carbon sorbents.     

油页岩灰渣提取硅酸钠制备纳米二氧化硅

以油页岩灰渣提取的硅酸钠为原料,采用溶胶-凝胶法并结合多种纳米粉体分散技术,制备了分散性好、粒径均一的纳米SiO2,其平均粒径约为10 nm。 制备过程中聚乙二醇（PEG）的加入能够有效的降低纳米SiO2的表面能,减少粒子的团聚, PEG的最佳浓度为3.0%;超声振荡的空化作用所释放出的巨大冲击波和微射流,能有效地击散纳米SiO2团聚体,其最佳超声时间为0.5 h;硅酸湿凝胶与正丁醇共沸蒸馏能有效脱除凝胶中的水,防止干燥过程中颗粒间硬团聚。     

PEG和PVP改性溶胶-凝胶二氧化硅减反膜的对比

聚乙二醇(PEG)和聚乙烯吡咯烷酮(PVP)对溶胶-凝胶二氧化硅减反膜的结构和激光损伤阈值(LIDT)有不同的影响.动态光散射、透射电镜(TEM)以及小角X射线散射实验表明:PEG能够促进二氧化硅颗粒的生长并增加团簇生长的一致性.然而,在PVP改性的溶胶中,Si―OH与PVP之间氢键作用制约了二氧化硅颗粒的生长.此外,多重分形谱(MFS)分析表明,PEG可以提高氧化硅薄膜的均匀性,PVP却降低了薄膜的均匀性,因此,PEG改性的氧化硅薄膜的抗激光损伤性能增强,而PVP改性的氧化硅薄膜的抗激光损伤性能被削弱.固体29Si魔角旋转核磁共振(MASNMR)结果表明,PEG能够提高Si―O四面体缩聚程度并改善薄膜的表面分形结构,PVP则相反,导致了PEG改性的氧化硅薄膜与PVP改性的氧化硅薄膜具有不同的抗激光损伤性能.     

Preparation of poly(ethylene glycol)-modified poly(amido amine) dendrimers encapsulating gold nanoparticles and their heat-generating ability

Loading of HAuCl4 in poly(amido amine) G4 dendrimers having poly(ethylene glycol) (PEG) grafts at all chain ends and subsequent reduction with NaBH4 yielded PEG-modified dendrimers encapsulating gold nanoparticles (Au NPs) of ca. 2 nm diameter. The Au NPs held in the dendrimers were stable in aqueous solutions and dissolved readily, even after freeze-drying. Despite their small particle size, the heat-generating ability of Au NPs held in the dendrimer was comparable to that of widely used Au NPs with ca. 11 nm diameter under visible light irradiation. The observed excellent colloidal stability, high heat-generating ability and their biocompatible surface confirm that the PEG-modified dendrimers encapsulating Au NPs are a promising tool for photothermal therapy and imaging.     

Structure‐Based Rational Design of Prodrugs To Enable Their Combination with Polymeric Nanoparticle Delivery Platforms for Enhanced Antitumor Efficacy

Drug‐loaded nanoparticles (NPs) are of particular interest for efficient cancer therapy due to their improved drug delivery and therapeutic index in various types of cancer. However, the encapsulation of many chemotherapeutics into delivery NPs is often hampered by their unfavorable physicochemical properties. Here, we employed a drug reform strategy to construct a small library of SN‐38 (7‐ethyl‐10‐hydroxycamptothecin)‐derived prodrugs, in which the phenolate group was modified with a variety of hydrophobic moieties. This esterification fine‐tuned the polarity of the SN‐38 molecule and enhanced the lipophilicity of the formed prodrugs, thereby inducing their self‐assembly into biodegradable poly(ethylene glycol)‐block‐poly(d,l ‐lactic acid) (PEG‐PLA) nanoparticulate structures. Our strategy combining the rational engineering of prodrugs with the pre‐eminent features of conventionally used polymeric materials should open new avenues for designing more potent drug delivery systems as a therapeutic modality.     

Interaction between poly(ethylene glycol) and water as studied by differential scanning calorimetry

The interaction between poly(ethylene glycol) (PEG) and water was studied by differential scanning calorimetry (DSC). The DSC curves of PEG–water systems were classified into three groups according to the difference in molecular weight. The melting peaks of eutectic mixture appeared for PEG with molecular weight higher than 1000. The eutectic point temperature shifted to higher temperatures and the eutectic point composition shifted to lower concentrations of PEG with increasing molecular weight. The maximum hydration number per ethylene glycol (EG) unit was estimated as 1.6, 2.4, and 3.3 for samples with molecular weights 400, 1540, and 70,000, respectively. No thermal change was found in PEG1540‐water system for a narrow weight fraction range of 0.585–0.605 for overall measuring temperatures due to perfect supercooling. The glass transition temperature shifted to higher temperatures with increasing molecular weight of PEG. A modified Flory–Huggins equation was used to fit curves for experimental liquidus data in phase diagrams. © 2001 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 39: 496–506, 2001     

Synthesis of poly(ethylene glycol)/polypeptide/poly(D,L‐lactide) copolymers and their nanoparticles

Core‐shell structured nanoparticles of poly(ethylene glycol) (PEG)/polypeptide/poly(D ,L ‐lactide) (PLA) copolymers were prepared and their properties were investigated. The copolymers had a poly(L ‐serine) or poly(L ‐phenylalanine) block as a linker between a hydrophilic PEG and a hydrophobic PLA unit. They formed core‐shell structured nanoparticles, where the polypeptide block resided at the interface between a hydrophilic PEG shell and a hydrophobic PLA core. In the synthesis, poly(ethylene glycol)‐b‐poly(L ‐serine) (PEG‐PSER) was prepared by ring opening polymerization of N‐carboxyanhydride of O‐(tert‐butyl)‐L ‐serine and subsequent removal of tert‐butyl groups. Poly(ethylene glycol)‐b‐poly(L ‐phenylalanine) (PEG‐PPA) was obtained by ring opening polymerization of N‐carboxyanhydride of L ‐phenylalanine. Methoxy‐poly(ethylene glycol)‐amine with a MW of 5000 was used as an initiator for both polymerizations. The polymerization of D ,L ‐lactide by initiation with PEG‐PSER and PEG‐PPA produced a comb‐like copolymer, poly(ethylene glycol)‐b‐[poly(L ‐serine)‐g‐poly(D ,L ‐lactide)] (PEG‐PSER‐PLA) and a linear copolymer, poly(ethylene glycol)‐b‐poly(L ‐phenylalanine)‐b‐poly(D ,L ‐lactide) (PEG‐PPA‐PLA), respectively. The nanoparticles obtained from PEG‐PPA‐PLA showed a negative zeta potential value of ?16.6 mV, while those of PEG‐PSER‐PLA exhibited a positive value of about 19.3 mV. In pH 7.0 phosphate buffer solution at 36 °C, the nanoparticles of PEG/polypeptide/PLA copolymers showed much better stability than those of a linear PEG‐PLA copolymer having a comparable molecular weight. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Decorated rods: a "bottom-up" self-assembly of monomolecular DNA complexes

Fluorescence correlation spectroscopy (FCS) and gel electrophoresis measurements are performed to investigate both the number and size of complexes of linear double-stranded DNA (dsDNA) fragments with 1:1 diblock copolymers consisting of a cationic moiety, branched polyethyleneimine (bPEI) of 2, 10, or 25 kDa, covalently bound to a neutral shielding moiety, poly(ethylene glycol) (PEG; 20 kDa). By systematically decreasing the bPEI length, the PEG grafting density along the DNA chain can be directly controlled. For 25 and 10 kDa bPEI-PEG copolymers, severe aggregation is observed despite the presence of the shielding PEG. Upon decreasing the bPEI length to 2 kDa, controlled self-assembly of monomolecular DNA nanoparticles is observed. The resulting complexes are in quantitative agreement with a theoretical model based on a single DNA encased in a dense PEG polymer brush layer. The resulting PEGylated complexes show high stability against both salt and protein and hence are of potential use for in vivo gene delivery studies.