Synthesis of novel carbohydrate based pyridinium ionic liquids and cytotoxicity of ionic liquids for mammalian cells

The large pool of naturally occurring carbohydrates with their diversity in chirality and structure led to the idea of a systematic investigation of carbohydrate based ILs. To this end, we investigated the influence of different ether groups, mainly methyl or ethyl ether, on the secondary OH groups as well as different configurations on physical properties such as melting point, thermostability and especially the influence on cell toxicity. For this investigation we chose α- and β-methyl-, β-allyl- and β-phenyl d-glucopyranose as well as four 1-deoxy-pentoses. In order to be able to classify the results, more ionic liquids with different structural motives were examined for cytotoxicity. Here, we present data that confirm the biocompatibility of such ILs consisting of naturally occurring molecules or their derivatives. The synthesized carbohydrate based ILs were tested for their suitability as additives in coatings for medical applications such as drug-eluting balloons.

The large pool of naturally occurring carbohydrates with their diversity in chirality and structure led to the idea of a systematic investigation of carbohydrate based ILs.     

叶酸修饰聚合物和脂质体药物载体及其靶向治疗的研究现状

背景:叶酸介导的靶向药物载体被广泛研究。目的:总结叶酸修饰靶向聚合物和脂质体药物载体的研究现状。方法:由作者应用计算机检索2000-01/2010-12Web of Science和CNKI数据库,选择叶酸修饰靶向聚合物和脂质体药物载体的相关文章,英文检索词为"folic acid,drug carriers,targeted delivery system,polymer,liposome",中文检索词为"叶酸,药物载体,靶向,聚合物,脂质体"。共纳入相关文献19篇进行综述。结果与结论:叶酸受体在多种肿瘤细胞表面过度表达,而在多数正常组织中的表达仅限于一些难于进入血液循环的上皮细胞顶膜。正因为叶酸受体表达的特性,叶酸受体天然配体——叶酸成为将药物靶向到肿瘤细胞的重要分子。叶酸具有与叶酸受体的高亲和力、低免疫原性等优点,这使得叶酸介导肿瘤靶向的研究得到迅速发展。含叶酸靶向的药物载体体系中,主要分为3大类:即人工合成高分子载体体系、脂质体和天然高分子载体体系。     

Assessment of the toxicity and biodegradation of amino acid-based ionic liquids

Amino acid-based ionic liquids (AAILs) are generally thought of as green solvents and widely used in many regions without systematic assessment of their effect on the environment or human health. In this work, a series of AAILs with different cations and amino acid anions were prepared and characterized, after which their microbial toxicity, phytotoxicity, and biodegradability were evaluated. The results showed that not all AAILs had low toxicity against microorganisms and that some AAILs were highly toxic towards the targeted microorganisms. The phytotoxic effect of the AAILs on rice (Oryza sativa L.) further demonstrated that AAILs should not be presumed to be non-toxic to plants. Moreover, the biodegradability tests showed that majority of AAILs were not satisfactorily biodegradable. In summary, not all AAILs are non-toxic or biodegradable, and their effect on the environment and human health must be assessed before their mass preparation and application.

This work evaluates the biodegradability, antimicrobial toxicity, and phytotoxicity of a series of amino acid-based ionic liquids (AAILs) with different cations and amino acid anions.     

Controlling the elasticity of polyacrylonitrile fibers via ionic liquids containing cyano-based anions

As the predominant precursor for high-performance carbon fiber manufacturing, the fabrication of polyacrylonitrile (PAN)-based composite fibers attracts great interest. Ionic liquids (ILs) have recently been investigated for melt-spinning of ultrafine PAN fibers. The plasticizing properties of ILs are significantly affected by the structure of ILs and can be influenced by electronegativity, steric effects, etc. Herein, we report a facile strategy to control the elasticity of the PAN/ILs fibers by tuning the anion structure of ILs. Particularly, the ILs containing nitrile-rich groups exhibited enhanced plasticizing effect and nucleating ability on dissolving PAN components, achieving highly stretchable PAN/ILs fibers.

Highly stretchable PAN/ILs fibers were fabricated through melt-spinning with ionic liquids containing cyano-based anions.

The unique properties of lightweight, excellent chemical resistance, and high strength make carbon fiber reinforced composites emerging materials for producing advanced functional composites for the aircraft, automobile, wind power, and sports equipment industries.^1,2 Despite the continuous market growth, the widespread use of carbon fibers is limited to high-end products primarily due to their tedious manufacturing steps and extensive capital investment. A substantial fraction of the expense results from the energy input needed to convert the fiber precursor into carbon fibers.^3–6 On the other hand, the mechanical performance (elastic modulus and tensile strength) of carbon fibers directly relies on the properties of the precursor.⁷ Polyacrylonitrile (PAN) is the preferred precursor employed for the manufacture of carbon fibers, leading the marketplace with a share of around 90%. PAN endows fibers with extraordinary mechanical characteristics and high production outputs.⁴ Meanwhile, carbon fibers derived from precursor fibers other than PAN or its derivatives exhibit considerably inferior mechanical performance.⁸ Thus, it is crucial to enhance the efficiency of the fiber spinning of PAN and its derivatives to cut down the total expense while keeping the merits of PAN as the precursor for carbon fibers.^9,10Generally, PAN-based fibers for high-strength carbon fibers manufacturing are spun through a solution spinning procedure, usually referred to as wet-spinning. Due to the high polarity of the nitrile group, solution spinning requires the use of highly polar solvents including dimethyl sulfoxide (DMSO), N,N-dimethylmethanamide (DMF), N-methyl-2-pyrrolidone (NMP), which accounts for the major production expense of PAN fibers.^6,11–16 As an alternative to solving this dilemma, the melt-spinning process has been developed as an efficient method for fabricating polymer nanofibers. In recent years, various polymers have been successfully melt-spun into ultrafine or nanometer fibers in melt forms.^17–20 This technique is particularly attractive for fabricating low-cost carbon fibers as it has a high manufacturing speed and eliminates the additional cost of solvent recycling.^21–25However, direct melt-spinning of PAN precursor is challenging largely owing to its high melting point (∼300 °C), at which temperature PAN begins to undergo thermal decomposition. External plasticization is frequently used to decouple the strong dipole–dipole interactions among the nitrile groups, which results in a decreased softening point below the PAN decomposition temperature. Examples of commonly used plasticizers include water, acetonitrile, dimethylformamide, alcohol, or co-solvents.²⁴ Ionic liquids (ILs), as potential “green solvents”, are ideal candidates for fiber impregnation not only because they possess negligible volatility, excellent thermal and chemical stability, and low toxicity,^26,27 but also is attributed to their brilliant capacity of dissolving natural and synthetic polymers,²⁸ such as cellulose,^29,30 chitosan,³¹ keratin,^32,33 silk,³⁴ and PAN³⁴ based on hydrogen bond theory.^35–37 The ILs are called the “designer solvents”,^38,39 as various properties and novel functionalities can be introduced to the material by accommodating a broad scope of component ions. Besides, many recent works have demonstrated the design of new series of ionic liquids with a low-cost synthesis route.^40–44 Although the major explorations of ILs have been inclined to focus on the development of the cationic structure modifications, the influence of cation chain length plays no major role during dissolution.⁴⁵ Meanwhile, the plasticizing properties of ILs are profoundly influenced by substituents of anions and may be systematically affected by the size, electronegativity, steric effects, etc.^46–48In this contribution, highly stretchable fibers composed of PAN and ILs were fabricated through the melt-spinning method. Four ILs with the same cation, 1-ethyl-3-methylimidazolium cation ([C₂mim]⁺), but different counter anions, from small halogen hydrogen-bond acceptors (Cl⁻/Br⁻) to larger polycyano anions (dicyanamide [N(CN)₂]⁻) and triacyanomethanide ([C(CN)₃]⁻), were incorporated with PAN to fabricate fibers (Fig. 1). Compared to the halides, the polycyano anions possess a higher electron-withdrawing ability, are expected to have stronger interaction with the PAN polymers, which can potentially lead to superior mechanical performance in the PAN/IL fiber composites. The main reason to select 1-ethyl-3-methylimidazolium cation is that the ILs with this cation have lower melting points and are less viscous than longer chain imidazolium ILs. In addition, the four ILs used in our papers are commercially available. The thermal analyses including thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to characterize the decomposition behavior, thermal stability as well as carbon yields of the PAN/ILs fibers. The morphological study and X-ray diffraction (XRD) were applied to determine the plasticizing effect and nucleating ability of each IL on the PAN composite fibers. The mechanical properties, particularly the elastic modulus and elongation at break, were investigated by tensile tests using an Instron 5943 universal testing machine. Besides, the regenerated PAN fibers made by removing ILs with deionized water were prepared for comparison.Open in a separate windowFig. 1Schematic illustration of the preparation of PAN/ILs composite fibers.Dry fine PAN powders (M_n = 52 290) were first mixed with IL, then heated to ∼160 °C under nitrogen to prepare homogenous PAN/ILs melts with a PAN : ILs = 30 : 70 weight ratio. The composite melts were then melt-spun to form uniform fibers (∼55 μm diameter) using a melt extruder following the procedures from the previous report.¹² One of the most important applications of PAN fibers is to be employed as the precursors for high-performance carbon fiber manufacturing. PAN fibers are converted to carbon fibers via oxidative cyclization/stabilization followed by carbonization. The cyclization/stabilization step converts –C N groups to cyclic –C N– and –C–N– groups and is typically carried out in the air in the temperature range of 200–300 °C. The carbonization temperature generally ranges from 400 to 800 °C.^49–51 The performance of the resultant carbon fibers is thus strongly associated with the cyclization process,^52,53 and the kinetics of cyclization can be modified by tuning the incorporated ingredients with PAN, such as carbon nanotubes, lignin, or cellulose nanocrystals,^54–56 which might facilitate the primary cyclization reaction and consequently increase the carbon yield.Before investigating the thermal behaviors of the PAN/ILs fibers, the thermal analysis of the pure ILs, PAN powders was conducted with TGA (scan ranges up to 800 °C under N₂ atmosphere) and DSC (scan ranges from −50 °C to 180 °C). As shown in the TGA plots (Fig. S3a^†), the ILs with halide anions exhibited 0 wt% carbon yield, and the nitrile-rich IL [C₂mim]TCM gave a similar carbon yield as PAN powders (∼30 wt%, Table S1^†), while [C₂mim]DCA''s ∼11 wt%. The DSC curves of the pure ILs and PAN powder were included in Fig. S2c and S3c,^† from where the crystallization and melting points of [C₂mim]Cl, [C₂mim]Br, and [C₂mim]DCA were obtained (Table S1^†). However, no peaks were observed in [C₂mim]TCM and PAN within the same scanning range. The polycyano anions: dicyanamide and triacyanomethanide are important because of their versatility in application to broad fields of materials science.⁵⁷ Due to their high contents of nitrile (–CN) moieties, higher carbon yields are expected in the corresponding hybrid fibers. The thermal decomposition of the four PAN/ILs fibers is shown in Fig. 2a, and surprisingly, high carbon yields were observed in all of the fiber samples, as PAN/[C₂mim]Cl: 50 wt%, PAN/[C₂mim]Br: 46 wt%, PAN/[C₂mim]DCA: 48 wt% and PAN/[C₂mim]TCM: 53 wt%. For comparison, TGA plots of the washed PAN fibers'' were included in Fig. S6a,^† which gave ∼43 wt% carbon yields. This indicates that a strong interaction was generated between the PAN and ILs during the extrusion processing, and besides the PAN, ILs also acted as the precursor and contributed to the high carbon yields. The strong interaction between PAN and ILs was also confirmed by the DSC curves of the composite fibers, Fig. 2c, as the melting/crystallization points of ILs can no longer be observed in the heat flow plots of PAN/ILs fibers.Open in a separate windowFig. 2(a) TGA curves of PAN/ILs fibers, (b) the plots of derivative weight vs. temperature of PAN/ILs fibers, (c) DSC curves of PAN/ILs fibers (d) the plots of derivative heat flow vs. temperature of PAN/ILs fibers, black line: [C₂mim]Cl; red line: [C₂mim]Br; blue line: [C₂mim]DCA; olive line: [C₂mim]TCM.The morphological features of PAN/ILs hybrid fibers were first examined by optical microscopy (Fig. S7^†) and scanning electron microscopy (SEM). The structures of the prepared PAN/[C₂mim]Cl and PAN/[C₂mim]TCM fibers before and after the PAN regeneration procedure are illustrated in Fig. 3 schematically. All samples exhibited a smooth surface morphology with an average diameter size of around 50 μm, indicating excellent compatibility of ILs with PAN. No significant difference was observed between the PAN/ILs fiber and the regenerated PAN fibers after the ILs'' removal procedure by deionized water.Open in a separate windowFig. 3SEM images of (a) PAN/[C₂mim]Cl fibers, (b) PAN/[C₂mim]TCM fibers, (c) washed PAN/[C₂mim]Cl fibers, (d) washed PAN/[C₂mim]TCM fibers, scale bars: 20 μm.As there are no clear differences obtained from thermal and morphological studies between the halide anions and polycyano anions ILs-based composite fibers, XRD was used to understand the interactions of PAN with ILs, which provides further insights into the investigation and evaluation of the plasticizing effect of the imidazolium-based ILs with nitrile-rich counter anions. The fibers were chopped into small pieces for the measurements and XRD patterns of four samples were shown in Fig. 4. The peak at 17.5° is the characteristic peak of PAN. The XRD results indicate that PAN/ILs with polycyano anions exhibited substantially higher crystallinity and slightly larger crystal size than the PAN/ILs with halide anions, as the higher intensity and sharper peaks shown in the patterns. Compared to ILs with halide anions, the multiple cyano moieties with high electron-withdrawing ability in polycyano anions are anticipated to induce more favorable interaction with PAN chains, which could benefit the dissolution and nucleation process. These enhanced plasticizing and nucleating effects result in higher crystallinity and slightly larger PAN crystal size in PAN/[C₂mim]DCA and PAN/[C₂mim]TCM fibers, as evidenced by the emergence of the sharper diffraction peaks. Our XRD results suggested that the PAN/ILs with polycyano anions fibers are expected to present better mechanical performance.Open in a separate windowFig. 4XRD comparison of four PAN-IL fibers: PAN/[C₂mim]Cl fibers (black line), PAN/[C₂mim]Br fibers (red line), PAN/[C₂mim]DCA fibers (blue line), PAN/[C₂mim]TCM fibers (olive line).The ability to preserve morphological integrity upon large deformation is critical to ensure a bulk material maintains reliable operation.⁵⁸ Compared with film-based devices, the fibrous ones are advantageous considering the convenience for packaging and thus particularly suitable for undersea applications.^59–62 Desired mechanical performance is also necessary to afford the materials to be employed in harsh environments, including transport, working, handling, and installation. However, it is challenging to achieve high elasticity in three-dimensional fibrous devices. Mechanical property evaluations of PAN/ILs fibers were carried out using an Instron 5943 universal testing machine. Twenty-five specimens were characterized for each fiber type (Fig. S4^†) and the representative strain–stress curves were included in Fig. 5a. The determination of Young''s modulus from the stress–strain curves is limited to the low-strain regime below 5% strain. The strain–stress curves of PAN/[C₂mim]Cl and PAN/[C₂mim]Br fibers exhibited typical ductile material features, in where the clear yield points (∼1.5% strain) and strain hardening were observed. On the other hand, PAN/[C₂mim]DCA and PAN/[C₂mim]TCM fibers show more elastomer-like features in the strain–stress curves with significantly higher elongation at break values, reaching 300% and 210%, respectively (Fig. 5b). A plausible explanation for this difference between PAN/ILs with halide anions and PAN/ILs with polycyano anions is that as the PAN and ILs exhibit excellent compatibility at PAN : ILs = 30 : 70 (wt%) ratio, the incorporation of ILs results in a fine PAN crystal distribution. The introduction of ILs with nitrile-rich groups showed a better plasticizing and nucleating ability than those ILs with halides anions. With high crystal nucleating density and fine crystal size, the mechanical properties of PAN/[C₂mim]DCA and PAN/[C₂mim]TCM fibers achieved a satisfactory enhancement. The higher stretchability exhibited in PAN/[C₂mim]DCA fibers is probably due to the stronger coordination ability of [N(CN)₂]⁻ than [C(CN)₃]⁻.⁵⁷ Besides, the performance of the regenerated PAN fibers was characterized for comparison (Fig. S5 and Table S2^†). A higher Young''s modulus and lower elongation at break values were obtained, which indicated that in a PAN/ILs fiber, the PAN provides mechanical robustness, while the IL offers sufficient elasticity.Open in a separate windowFig. 5(a) Representative strain–stress curves of PAN/IL fibers, black: [C₂mim]Cl/PAN fibers, red: [C₂mim]Br/PAN fibers, blue: [C₂mim]DCA/PAN fibers, olive: [C₂mim]TCM/PAN fibers, (b) Young''s modulus and elongation at break of PAN/ILs fibers.In this work, we present a robust methodology for fabricating highly stretchable PAN/ILs fibers via the melt-spinning technique using ILs with polycyano anions. The selection of different ILs could profoundly affect the properties of the PAN composite fibers. ILs containing strong electronegativity halide anions such as [C₂mim]Cl/[C₂mim]Br, and ILs with polycyano anions ([C₂mim]DCA/[C₂mim]TCM) which have high electron-withdrawing ability were screened to investigate their plasticizing effect on the PAN fibers. With 30 wt% PAN loading in the composite fibers, all four ILs exhibited excellent compatibility with PAN. The PAN/ILs fibers also showed high carbon yields, which even exceed that of the fresh and regenerated PAN fibers. This indicated a strong interaction was induced between the PAN chains and the ILs through the extruding procedure. Besides the PAN, the incorporated ILs were also attributed to the high carbon yields as the carbon precursors. In the tensile tests, in dramatic contrast to the brittle nature of PAN fibers, the PAN/ILs fiber samples with 70 wt% [C₂mim]DCA/[C₂mim]TCM ILs exhibited outstanding mechanical properties for large deformations (300%/210%). Compared to the PAN/[C₂mim]Cl and PAN/[C₂mim]Br fibers, which showed typical ductile material features, more elastomer-like featured strain–stress curves were observed in PAN/[C₂mim]DCA and PAN/[C₂mim]TCM fibers. These significantly enhanced mechanical performances can be attributed to the better plasticizing and nucleating ability of nitrile-rich ILs, which is supported by the results of higher PAN crystallinity and slightly larger crystal size from XRD patterns. This work demonstrated that rational incorporation with appropriate functional anions would not only extend the ongoing exploration of novel and versatile ILs but also help understand the correlation between the molecular structures of component ions and composite properties. The developed PAN/ILs fibers, which exhibit tunable and excellent mechanical properties, assure the material with promising prospects for extensive applications in various fields.     

Ultrasound radiation force enables targeted deposition of model drug carriers loaded on microbubbles.

A novel drug delivery vehicle that specifically targets using ultrasound radiation force (USRF) and biotin-avidin interactions is presented. Model vehicles consist of avidinated fluorescent nanobeads bound directly to the biotinylated lipid shells of preformed microbubbles. USRF was used to deflect the vehicle from the center of flow to a tube surface in order to facilitate receptor-ligand mediated adhesion. At wall shear stress levels commensurate with venous and arterial flow, USRF was used to direct the vehicles to a biotinylated tube surface. Subsequent high-pressure pulses fragmented the carrier, and molecular interactions induced deposition of the nanobeads on the wall. Targeting of nanobeads to the tube was molecularly specific and dependent on, in order of importance, vehicle concentration, wall shear stress, nanobead size, and insonation time. The observation that portions of the microbubble lipid monolayer shell remain attached to adherent nanobeads is important for future consideration of drug transport mechanisms. This versatile method of delivery is shown to enable targeted deposition of nanoparticles in shear flow and could be modified to carry therapeutic agents for controlled release in targeted delivery applications.     

两种药物控释载体的体外释药性能

药物控释载体可有效控制药物治疗剂量和药物在体内病灶部位的选择性释放，具有毒副作用低、给药剂量小、良好生物利用度、稳定性、更长的半衰期等特点，药物控释载体材料可分为生物可降解高分子聚合物材料和纳米磁性材料。高分子聚合物材料应用比较多的有聚乳酸及其共聚物和壳聚糖等，具有无毒、无害、优良的生物相容性、代谢产物无毒、能被生物体完全吸收等优点，与化疗药物结合制备的缓释微球，具有良好的缓释功能。磁性药物微球多采用纳米铁粒作为磁响应性材料，将具有磁性的超微磁粉与抗肿瘤药物共同包入人体白蛋白或其它高分子物质中，制成具有一定磁响应性能的载附抗癌药物的微球体，在体外磁场作用下可以实现靶向给药，是靶向治疗恶性肿瘤的一种新途径。然而，尽管药物控释载体的研究已经取得一定成果，但临床应用的药物制剂还不太多，加强剂型设计和制备技术的研究，研究和开发新的高性能药物载体及智能化药物释放体系将是靶向型药物控制释放体系研究的热点。     

Transport properties of protic and aprotic guanidinium ionic liquids

Ionic liquids (ILs) are a promising class of solvents, functional fluids and electrolytes that are of high interest for both basic as well as applied research. For further fundamental understanding of ILs and a successful implementation in technical processes, a deeper insight into transport properties and their interrelations is of particular importance. In this contribution we synthesised a series of mostly novel protic and aprotic ILs based on the tetramethylguanidinium (TMG) cation that is a derivative of the superbase guanidine. Different substitution patterns and anions from acids with broadly varied pK_a values were investigated. We measured general properties, such as thermal transitions and densities of these ILs, as well as their transport quantities by means of rheology, impedance spectroscopy and NMR diffusometry. Different models for the correlation of the transport properties, namely the Nernst–Einstein, Walden and Stokes–Einstein–Sutherland relations were applied. The deviation from ideal behaviour of fully dissociated electrolytes, often termed as ionicity, was quantified by the reciprocal Haven ratio, fractional Walden rule and ionicity obtained from the Walden plot. Velocity cross-correlation coefficients were calculated to gain further insight into the correlation between ion movements. Both protic and aprotic TMG ILs show transport properties comparable to other ILs with similar molecular weight and high ionicity values especially in contrast to other protic ILs. Lowest ionicity values were found for the protic ILs with smallest ΔpK_a values between constituting acid and base. This can either be explained by stronger hydrogen bonding between cation and anion or lower anti-correlations between the oppositely charged ions. These results aim to provide insight into the properties of this interesting cations class and a deeper understanding of the transport properties of ILs and their interrelations in general.

New protic and aprotic ionic liquids based on superbase cations show promising properties and enrich the field of cation classes     

Synthesis of novel functional ionic liquids and their application in biomass

A series of dicationic ionic liquids (ILs) including [PF₆][(PYR)C₄(MIM)][Cl], [PF₆][(PYR)C₄(PYR)][Cl], [PF₆][(PYR)C₅(MIM)][Cl], and [PF₆][(PYR)C₅(PYR)][Cl], and monocationic ILs including [(PYR)C₄Cl][PF₆], [(PYR)C₅Cl][PF₆], [(MIM)C₂COOH][PF₆] and [(PYR)C₂COOH][PF₆] were synthesized. Their thermal stability and melting points were determined. Their solubility with organic solvents and the miscibility with water were investigated. These functional ILs are hydrophilic at high temperatures and they are hydrophobic at low temperatures, which enable the effective isolation of the resulting reducing sugar. High yields of reducing sugar were obtained for corn stalk after 8 h (20.73%) and potato starch after 6 h (72.50%) by the treatment with the mixture of [PF₆][(PYR)C₄(PYR)][Cl] and [(PYR)C₂COOH][PF₆]. The reuse of dicationic and monocationic ILs was successfully performed and no significant reduction in yields of reducing sugar was observed. These functional ILs have important implications in the design of homogeneous and heterogeneous systems with water and organic solvents, which could be used to satisfy some specific applications.

A series of dicationic and monocationic ionic liquids (ILs) were synthesized and investigated and it was found that these functional ILs have important implications in the design of homogeneous and heterogeneous systems.     

含聚乙二醇两亲性聚合物及其胶束用作药物载体的理论研究及应用潜力

目的:对含聚乙二醇的两亲性聚合物种类、合成及在药物载体领域的应用进行综述.资料来源:应用计算机检索SCI-Expanded、EI Compendex和中国期刊全文数据库2000-01/2009-07关于含聚乙二醇的两亲性共聚物分类、合成及其胶束在药物载体领域研究的相关文献.资料选择:初检得到616篇文献,阅读标题和摘要进行初筛,以含聚乙二醇的两亲性共聚物的分类与合成是否全面细致,对于自主装形成胶束的影响因素是否有相当的代表性及前沿性为纳入标准,共保留31篇中英文文献进行进一步分析.结局评价指标:含聚乙二醇的两亲性共聚物分类、合成、载药机制:共聚物胶束在药物载体领域中的应用情况.结果:①星型共聚物能提高胶束稳定性,但臂数太多,有可能导致载药量降低.②共聚物中引入特定的基团有利于药物与载体的结合;连接靶向基团能使体系提供靶向运送特性.③共聚物中聚乙二醇链的长度和密度与胶束化性能有关,改变聚乙二醇长度和密度可以获得较长时间在体内循环的聚合物胶束.结论:含聚乙二醇的两亲性共聚物在医学载药领域和分离技术方面具有优越的应用潜力.     

Building an electrochemical series of metals in pyrrolidinium-based ionic liquids

An electrochemical series of pyrrolidinium-based ionic liquids is established by designing a redox system where only one kind of anion is present in the electrolyte and metal ions are supplied by anodic dissolution. This is the first report where an electrochemical series is established in pure ionic liquids.

An electrochemical series of pyrrolidinium-based ionic liquids is established by designing a redox system where only one kind of anion is present in the electrolyte and metal ions are supplied by anodic dissolution.

Ionic liquids, salts in the liquid state, are typically a family of molten salts solely comprised of cations and anions with a low melting point below 100 °C. The unique physicochemical properties of ionic liquids such as low vapor pressure, non-volatility, good thermal stability, high ionic conductivity and a wide electrochemical window make ionic liquids an alternative to conventional organic and aqueous electrolytes.¹ Meanwhile, almost unlimited variations of ionic liquids can be synthesized by combining numerous kinds of cations and anions. These features of ionic liquids have enabled the implementation of various technologies, and particularly the redox chemistry of various metals in ionic liquids has been utilized in such applications as electrodeposition, electrowinning, cementation, corrosion, metal-air batteries and redox batteries.^2–10 Recently, some unusual findings where a less noble metal is deposited on a more noble metal by electroless deposition, that is, a galvanic displacement reaction, have been reported.^11–13 As Lahiri et al. pointed out, these kinds of galvanic displacement reactions could be triggered by forming metal ion complexes with the anions of ionic liquids, making the redox potentials in ionic liquids different to those of metal complexes in aqueous solution.¹³An electrochemical series in an aqueous system has been well established, and is available in the form of a standard electrode potential database.¹⁴ Standard electrode potential is defined as the measure of the individual potential of reversible electrodes at a standard state with ions at an effective concentration of 1 M at the pressure of 1 atm, and is usually measured or calculated at 25 °C. Similarly, the galvanic series was also established for the determination of the nobility of metals in saltwater.¹⁵ In contrast, there is no universal electrochemical series in the case of ionic liquids. Because the combination of metal and ionic liquid is very selective for the specific purpose of the aforementioned applications where the redox chemistry of metals in ionic liquids is utilized,¹⁶ Abbott et al.''s electrochemical series for deep eutectic solvents would be the only report of its kind.¹⁷ They established an electrochemical series of various redox couples in ethaline that is the 1 : 2 mixture of choline chloride and ethylene glycol. Although their approach was systematic and extensive, there would be some limitations in that ethaline was not a pure compound but a mixture and adopted metal salts consisted of various unspecified anions. Because the metal-ion speciation in this case is complex and inconsistent, it would be desirable to make a redox system as simple as possible. Therefore, we design a redox system where only one kind of anion is present in electrolyte and metal ions are supplied by anodic dissolution for the establishment of an electrochemical series in ionic liquids. In this study, an attempt to build the electrochemical series of various metals is made in pyrrolidinium-based ionic liquids by using a ferrocene/ferrocenium (Fc/Fc⁺) internal reference at room temperature.The schematic structure of the cation and anions constituting two ionic liquids (1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide and 1-butyl-1-methylpyrrolidinium bis(fluorosulfonyl)imide) adopted for this study is presented in Scheme 1. 1-Butyl-1-methylpyrrolidinium cation has a few different abbreviations (BMPyr, BMP or Py_1,4) in literature. Two kinds of anions (bis(fluorosulfonyl)imide and bis(trifluoromethylsulfonyl)imide) also have various abbreviations where we prefer to use Nf₂ (rather than FSA) for bis(fluorosulfonyl)imide, and NTf₂ (rather than TFSI, Tf₂N, and TFSA) for bis(trifluoromethylsulfonyl)imide.Open in a separate windowScheme 1Schematic structures of (a) 1-butyl-1-methylpyrrolidinium [BMPyr]⁺, (b) bis(fluorosulfonyl)imide [Nf₂]⁻, and (c) bis(trifluoromethylsulfonyl)imide [NTf₂]⁻. Fig. 1 shows a comparison of electrochemical window of [BMPyr] [NTf₂] and [BMPyr] [Nf₂] ionic liquids in neat condition. The cathodic and anodic electrochemical limit is commonly defined at the voltage where a specific current density is reached. The cutoff current density is usually and arbitrarily selected from 0.1 to 1.0 mA cm⁻².¹⁸ [BMPyr] [NTf₂] exhibits cathodic stability limit and anodic stability limit up to −3.5 and 2.4 V, respectively, and consequently the electrochemical window is 5.9 V. [BMPyr] [Nf₂] exhibits cathodic stability limit at −2.5 V and anodic stability limit at 2.8 V, showing the electrochemical window of 5.3 V. No marked reduction or oxidation currents of the electrolytes were detected within this range. All potentials reported herein are displayed on the Fc/Fc⁺ potential basis, of which stability during storage or cyclic voltammetry in the ionic liquids were confirmed in Fig. S1.^† Particularly, [BMPyr] [NTf₂] exhibits more negative cathodic stability limit than [BMPyr] [Nf₂] whereas [BMPyr] [Nf₂] displays a little more extended anodic stability limit than [BMPyr] [NTf₂]. In general, the electrochemical window of ionic liquids depends on cation/anion combination, water content, and other factors. The decomposition of corresponding cations and anions of ionic liquids affects cathodic and anodic limits, respectively.^19–21 Considering that [BMPyr] [NTf₂] and [BMPyr] [Nf₂] have the same cation, it is surprising that there is a definite difference in cathodic stability. However, Ong et al. have demonstrated that the cathodic stability is influenced not by cation alone but by the combination of cation and anion.¹⁸Open in a separate windowFig. 1Electrochemical window of [BMPyr] [NTf₂] and [BMPyr] [Nf₂] (gold working electrode in neat condition at a scan rate of 10 mV s⁻¹ at room temperature).Metal ions are usually introduced to ionic liquids by dissociating metal salts such as metal chloride.^3,17 Because the solubility of metal salts in ionic liquids is generally much lower than that in aqueous solutions, as high as 1 M of metal ion concentration cannot be achieved for measuring standard electrode potential. Therefore, we applied an anodic dissolution to the preparation of a designated concentration of metal ions in the ionic liquids.^22,23 Once a linear sweep voltammetry is conducted for a specific couple of metal and ionic liquid, the required amount of metal ions for a designated concentration (0.1 mM) is calculated based on Faraday''s law and the corresponding upper limit of dissolution potential is determined. Fig. 2 shows the linear sweep voltammetry (LSV) for five metals in [BMPyr] [NTf₂] and [BMPyr] [Nf₂] at room temperature. All of the metals used as working electrodes can be electrochemically oxidized in [BMPyr] [NTf₂] and [BMPyr] [Nf₂]. More anodic currents were observed in [BMPyr] [Nf₂] than [BMPyr] [NTf₂] because Nf₂ anion based ionic liquids have a higher conductivity and lower viscosity than NTf₂ anion based compounds.²⁴ The amount of dissolved metals required for 0.1 mM concentration and their corresponding dissolution potential are calculated based on Faraday''s law (ESI^†) and Fig. 2, and tabulated in Open in a separate windowFig. 2Anodic linear sweep voltammetry of five metals in (a) [BMPyr] [NTf₂] and (b) [BMPyr] [Nf₂].The amount of dissolved metals and their corresponding upper limit of dissolution potential for 0.1 mM concentration

靶向癌胚抗原载药纳米超声造影剂体外抑制卵巢癌细胞生长

目的 制备靶向癌胚抗原（CEA）载药相变型PLGA纳米粒（Ab-PTX-NPs）,探讨该纳米粒的体外寻靶及抑制肿瘤细胞生长的效能。方法 乳化溶剂挥发法联合碳二亚胺法制备靶向CEA载紫杉醇纳米粒（Ab-PTX-NPs）,采用马尔文粒径分析仪检测其粒径大小。采用高效液相色谱法检测紫杉醇包封率及载药量,恒温摇床透析法检测该纳米粒体外释药特征。激光共聚焦显微镜及流式细胞术观察该纳米粒体外寻靶情况,CCK-8试剂检测卵巢癌细胞存活率。结果 制备的Ab-PTX-NPs粒径为（397.70±99.95）nm,紫杉醇包封率及载药量分别为（67.26±4.15）%和（6.31±0.39）%。抗CEA单克隆抗体与纳米粒连接率为（92.74±5.75）%。共聚焦显微镜下观察到靶向组卵巢癌SKOV3细胞周围见较多造影剂黏附,流式细胞术测得靶向组细胞平均荧光强度明显高于其余各组（P<0.05）,CCK-8试剂法测得靶向组在24 h时,细胞存活率高于纯药组（P<0.05）,而低于无靶组（P<0.05）,当48 h时,靶向组与纯药组细胞存活率差异无统计学意义（P>0.05）。结论 成功制备靶向CEA载药相变型PLGA纳米粒,该纳米粒经低功率聚焦超声治疗仪（LIFU）致相变后可明显增强超声显影,且载药量高,释药快,靶向能力强。     

载硫化铋及阿霉素靶向相变型纳米粒多模态显像及联合治疗卵巢癌体外实验

目的 制备叶酸靶向载硫化铋(Bi2S3)与阿霉素(DOX)相变型纳米粒(FBS-PFP-PLGA@DOX),观察其基本性能、体外多模态显像及光热联合治疗体外卵巢癌的效果.方法 以双乳化法制备FBS-PFP-PLGA@DOX,检测其理化性质;观察其体外多模态显像;采用近红外激光辐照FBS-PFP-PLGA@DOX并实时记...     

Synthesis of plasmonic Fe/Al nanoparticles in ionic liquids

Bottom-up and top-down approaches are described for the challenging synthesis of Fe/Al nanoparticles (NPs) in ionic liquids (ILs) under mild conditions. The crystalline phase and morphology of the metal nanoparticles synthesized in three different ionic liquids were identified by powder X-ray diffractometry (PXRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), selected-area electron diffraction (SAED) and fast Fourier transform (FFT) of high-resolution TEM images. Characterization was completed by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) for the analysis of the element composition of the whole sample consisting of the NPs and the amorphous background. The bottom-up approaches resulted in crystalline FeAl NPs on an amorphous background. The top-down approach revealed small NPs and could be identified as Fe₄Al₁₃ NPs which in the IL [OPy][NTf₂] yield two absorption bands in the green-blue to green spectral region at 475 and 520 nm which give rise to a complementary red color, akin to appropriate Au NPs.

Fe/Al NPs of the right size mimic with their red color the electronic surface structure of Au NPs.     

Synthesis and properties of novel ammonium-based room-temperature gemini ionic liquids

Ammonium-based room-temperature asymmetrical gemini ionic liquids, 1-trimethylammonium-3-(pyridinium)propane bisdicyanamide ([N₁₁₁C₃Py][DCA]₂) and 1-trimethylammonium-3-(1-methylpiperidinium)propane bisdicyanamide ([N₁₁₁C₃MPi][DCA]₂) were respectively synthesized and structurally characterized by ¹H NMR and ¹³C NMR. Thermal stability of the gemini ionic liquids was determined by thermogravimetric analysis under a pure nitrogen atmosphere. Densities and viscosities of pure GILs and their binary mixtures with acetonitrile (MeCN) were investigated over the entire range of mole fractions at various temperatures, from 288.15 to 333.15 K, under atmospheric pressure. Moreover, the excess molar volumes (V^E_m) and the viscosity deviations (Δη) of the binary mixtures were evaluated and well fitted to the Redlich–Kister polynomial expression. The negative values of V^E_m and Δη result from strong self-association and interaction between the gemini ionic liquid molecules and MeCN. Results are discussed in terms of molecular interactions and structures.

Ammonium-based asymmetrical gemini ionic liquids, 1-trimethylammonium-3-(pyridinium)propane bisdicyanamide and 1-trimethylammonium-3-(1-methylpiperidinium)propane bisdicyanamide were respectively synthesized and characterized by ¹H NMR and ¹³C NMR.     

Photostability and photocatalytic degradation of ionic liquids in water under solar light

The aim of this work is to study, (i) the photostability of different imidazolium and pyridinium ionic liquids (ILs) in water under solar light; and (ii) the photocatalytic degradation of those ILs in water with TiO₂ under solar light. The effects of the type of cation and anion as well as the length of the cationic chain of the imidazolium ILs have been analyzed. These imidazolium-based ILs show high solar stability, slightly decreasing as the length of the cationic chain increases. The anion plays a main role in the stability of ILs under solar light, decreasing in the case of hydrophobic anions. The kind of head group (pyridinium or imidazolium) or the presence of functional groups (allyl, OH) also influence the solar light stability. DFT calculations on the fundamental and excited electronic states of the ILs were carried out to obtain a deeper insight on their photostability. In the case of the photocatalytic degradation of the ILs, complete conversion was achieved for all the ILS tested but mineralization reached 80% at the most. The rate of degradation increased with the length of the alkyl chain while the anion showed little effect. The pyridinium-based IL tested was the easiest to breakdown.

The aim of this work is to study, (i) the photostability of different imidazolium and pyridinium ionic liquids (ILs) in water under solar light; and (ii) the photocatalytic degradation of those ILs in water with TiO₂ under solar light.     

Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle-skin interaction.

The influence of liposome composition, size, lamellarity and charge on the (trans)dermal delivery of tretinoin (TRA) was studied. For this purpose we studied both multilamellar (MLV) or unilamellar (UV) liposomes. Positively or negatively charged liposomes were obtained using either hydrogenated (Phospholipon90H) or non-hydrogenated soy phosphatidylcholine (Phospholipon90) and cholesterol, in combination with stearylamine or dicetylphosphate. Liposomal formulations were characterized by transmission electron microscopy (TEM) and optical and light polarized microscopy for vesicle formation and morphology, and by dynamic laser light scattering for size distribution. In order to obtain more information about the stability and the thermodynamic activity of the liposomal tretinoin, TRA diffusion through a lipophilic membrane was investigated. The effect of the vesicular incorporation of tretinoin on its accumulation into the newborn pig skin was also studied. The experiments were performed in vitro using Franz cells in occlusive conditions and were compared to three different controls. The tretinoin amount delivered through and accumulated in the several skin layers was detected by HPLC. Furthermore, TEM in combination with osmium tetroxide was used to visualize the skin structure after the liposomal administration. Overall obtained results showed that liposomes may be an interesting carrier for tretinoin in skin disease treatment, when appropriate formulations are used. In particular, negatively charged liposomes strongly improved newborn pig skin hydration and TRA retention, though no evidence of intact vesicle penetration was found.     

药物缓释载体材料类型及其临床应用

目的:文章对目前国内外几种重要载体材料的临床应用情况进行了阐述.方法:作者以"药物载体,缓释材料,生物降解"为检索词,在中国期刊全文数据通据库(CNKI:1989/2010),采用电子检索的方式对所有相关文献进行了详细检索.排除Meta分析及重复性研究,最终入选20篇文献进入结果分析.结果:生物降解性合成高分子材料安全、可靠,有良好的生物相容性,成为药物缓释载体的首选材料;壳聚糖作为药物缓释载体在减少给药次数,降低药物毒副作用,提高药物疗效等方面具有重要作用;纳米纤维载体可明显增强药物缓释效果;纤维蛋白生物相容性好,是良好的药物缓释载体.结论:药物控制释放体系在机体内可以显示出被动靶向以及缓释等多种优点,它是药物缓释体系的重要组成部分,也是影响药效的主要因素.     

High-throughput toxicity screening of novel azepanium and 3-methylpiperidinium ionic liquids

Ionic liquids (ILs) have been employed as potentially environmentally friendly replacements for harmful organic solvents, but have also been studied for their use in bioelectrochemical applications, such as in microbial electrochemistry for bioenergy production, or in industrial biocatalysis. For these processes, low microbial toxicity is important and there is a growing need for microbial toxicology studies for novel ILs. In this study, we report initial toxicity data for novel ILs, based on azepanium and 3-methylpiperidinium cations. Agar disc diffusion assays are used, along with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) determinations, to obtain rapid and inexpensive initial toxicity data for these novel ILs against Escherichia coli and Staphylococcus epidermidis. Many of the novel ILs characterised possess low microbial toxicity relative to well-studied ILs, highlighting their potential for further study in applications where this is a desirable property.

Ionic liquids have been employed as potentially environmentally friendly replacements for organic solvents, but have also been studied for their use in bioelectrochemical applications, such as bioenergy production, or in industrial biocatalysis.