1- Introduction

2- Experimental section

3- Results and discussion

4- Conclusions

References

Abstract

In this paper, a targeting hyaluronic acid (HA)/mesoporous silica nanoparticle (MSN) based drug delivery system (DDS) with dual-responsiveness was prepared for cancer therapy. To avoid the side reaction between the anti-cancer drug doxorubicin hydrochloride (DOX) and HA, host-guest interaction was applied to fabricate the DDS named DOX@MSN-SS-N=C-HA. The “nanocontainer” MSN was modified with benzene ring via both pH-sensitive benzoic imine bond and redox-sensitive disulfide linkage. When DOX was loaded in the pores of MSN, the channels were then capped by the “gatekeeper” β-CD grafted HA (HA-g-CD) through host-guest interaction between β-CD and benzene. HA endowed the drug carriers with the targeting capability in CD44 over-expressed cancer cells. After cellular uptake, the carriers could rapidly release DOX for cell apoptosis due to both the hydrolysis of benzoic imine bond at low pH and the cleavage of disulfide bond at a high concentration of glutathione (GSH) intracellular. In vitro drug release studies and in vitro cytotoxicity studies were taken to investigate the dual-responsiveness of the carriers. And the CD44-receptor mediated cancer cell targeting capability was investigated as well. In conclusion, the targeted dual-responsive complex DDS fabricated through host-guest interaction has promising potential in cancer therapy.

Introduction

Chemotherapy remains one of the major therapeutic approaches applied to treat cancer in clinic. However, the disadvantages of traditional chemotherapeutic drugs such as unfavorable pharmacokinetics, poor biodistribution and lack of selectivity for target tissues reduce the utilization of the drugs and cause serious side effects [1]. To tackle these problems, anti-cancer drug delivery systems (DDSs) based on nanotechnology have been introduced and developed rapidly in recent decades [1–4]. DDSs such as liposomal daunorubicin (DaunoXome), pegylated liposomal doxorubicin (Doxil), albumin nanoparticle based Nan-paclitaxel (Abraxane) and polymeric micelle paclitaxel (GenexolPM) have already been approved for clinical treatment of cancer [3,4]. These nanosized DDSs can be accumulated in tumor tissues more easily via enhanced permeability and retention (EPR) effect to improve the pharmacokinetics and biodistribution of the drugs, as well as to reduce their side effects [5]. Though the commercial DDSs represented by the liposomal doxorubicin can overcome part of the shortcomings of traditional anticancer drugs, they cannot or only modestly improve patients’ overall survival [3,6–9]. Therefore, more efforts are needed to develop novel advanced DDSs. The properties including controlled drug release based on stimuli- sensitivity [10,11] and ligand-mediated active cancer targeting [12–15] introduced make the newly reported DDSs with better therapeutic effects [1–4]. During the past decade, mesoporous silica nanoparticle (MSN) based DDSs have attracted considerable attention from scientists worldwide [16,17]. MSNs can be simply synthesized with tunable size, shape, pore size and volume [17,18], and are easy surface functionalization [16]. These advantages, as well as the high drug loading capacity and good biocompatibility, ensure that MSNs are excellent choices for designing safe and efficient drug carriers [16–18].

1- Introduction

2- Material and methods

3- Results and discussion

4- Conclusions

References

Abstract

Mesoporous silica nanoparticles with folic acid (MSN−COOH-Tet-HBP-FA) are able to mediate targeting and have a pH stimulation response character, and therefore have been successfully synthesized as vectors for antitumor drug delivery. The model drug is tetrandrine (Tet). The chemical structure and properties of these NPs were characterized through systematic characterization analyses. Their drug loading capacity was significantly improved through carboxy modification (26.86 % in max), and they exhibited pH-dependent drug release profiles(“zero pre-release” within 20 h in a normal physiological environment). In vitro cytotoxicity and cell uptake of the as-synthesized NPs in Hela and A549 cells were also evaluated, and exhibited high cytotoxicity and cell-targeted uptake capacity. It was concluded that MSN−COOH-Tet-HBP-FA could be used as a promising drug delivery system for cancer therapy.

Introduction

Cancer is currently considered to be a leading factor that threatens human lives, and chemotherapy remains one of the most common methods used for cancer treatment. However, traditional drugs are nonspecific and cannot discriminate cancer cells and normal cells, which not only limits the accumulation of drugs in tumor cells, but also leads to systemic toxicity and adverse side effects. In order to improve the efficacy of chemotherapy, many studies have been devoted to the development of tumor-targeted nanocarriers, which can be used to control the delivery of antitumor drugs. Using the enhanced permeation and retention (EPR) effects, researchers have developed multiple nanocarrier platforms, including liposomes, polymer nanoparticles, nano-micelles, and dendrimers, which are used to delivery anticancer drugs into tumor tissues. However, the EPR effect is not efficient enough to eradicate the side effects of cytotoxic drugs and to exert the anticancer therapy selectively in cancer cells. In order to enhance the targeting and tumoral uptake ability, the external surface of nanocarrier is often modified with various ligands, which can significantly enhance the interaction between the cancer cells and the nanocarriers[. Targeted agents typically include antibodies (such as monoclonal antibodies), peptides (such as Arg-Gly-Asp (RGD)), and small molecule compounds (such as folic acid).

Plastic concrete is used in the manufacture of cut off wall and its mechanical properties is important for performance of dam. In this paper, in order to investigate the durability and mechanical properties of plastic concrete, uniaxial and triaxial compressive strength tests were performed on plastic concrete specimens in different ages (7, 14, 28, 56 and 90 days) and different percentage of replacement cement by nano silica (0, 1.5, 3, 4.5 and 6%) and compressive strength, the stress–strain behavior, elastic modulus, shear strength parameters of plastic concrete have been evaluated. According to the result, as the age of the specimen increases, elastic modulus, compressive strength and triaxial strength of the plastic concrete enhances. Furthermore, although by increasing the amount of nano silica the strength parameters of plastic concrete are improved and workability of concrete is reduced and the amount of elastic modulus of the specimen is almost constant. The results of shear strength parameters also show that the addition of up to 3% of nano silica increases the cohesion and internal friction angle decreases and with over 3% nano silica this trend is reversed and cohesion decreases and friction angle increases.

Introduction

The rheology and permeability of various concrete and advantage of nano material as a partial replacement for cement is well established in previous papers [1–11]. Besides, plastic concrete of cut-off wall is buried inside the soil in geotechnical project [12–14]. Two main attributes are necessary. Firstly, they should have enough strength to bear the weight of the dam body and secondly, a low elastic modulus that works seamlessly integrated with the surrounding environment soil [15–19]. If the elastic modulus is much higher than the surrounding soil of cut-off wall, soil and wall do not have load bearing capacity for unified action and cut-off wall will be cracked and its performance will be lost. The high elastic modulus of normal concrete is the reason for not using normal concrete in making the cut-off wall. As a result, plastic concrete satisfies both of the above conditions, and so is used to construct a cut-off wall. The water to cement ratio of plastic concretes is usually considered in the range of 1.5–4 to achieve the low elastic modulus; however, in normal concretes, this range varies between 0.35 and 0.65 [16,20–24]. In the previous researches [25,26], the compressive strength parameters of plastic concrete are investigated by performing uniaxial compressive strength. They showed that the compressive strength of concrete specimens depends on various parameters such as cement and bentonite content, aggregate size and specimen age.

1- Introduction

2- Experimental

3- Results and discussion

4- Conclusions

References

Abstract

The chiral separation of baclofen (Bac) was obtained by nano-liquid chromatography tandem mass spectrometry (nano-LC–MS/MS) using a 100 μm I.D. fused silica capillary column packed with silica particles chemically modified with vancomycin. Various experimental parameters, such as composition (buffer concentration, water content, organic modifier) and pH of the mobile phase and sample solvent were investigated for method optimization. In order to increase the sensitivity an on-column focusing procedure was applied. Acceptable separation of Bac enantiomers was obtained in less than 11 min eluting in isocratic mode, with 90:10 MeOH/water (v/v) containing 10 mM ammonium acetate at pH 4.5. These optimized experimental conditions were applied to the analysis of human plasma samples spiked with racemic mixture of Bac. The use of a Buckypaper disc as sorbent membrane allows one to recover both enantiomers with yields ≥ 65%. The method was fully validated, following the identification criteria of the European Commission Decision 2002/657/EC.

Introduction

Still today, chirality is a key topic of research because of the overriding importance of enantiomers in various areas such as environmental, food, pharmaceutical, and above all human health science. In this regard, it is worth mentioning that more than a half of the produced and prescribed drugs have one or more chiral centres [1] and, as a result, they exhibit one or more couples of enantiomers. It is well-known that drug/receptor interaction is greatly stereoselective. Consequently, only one of the two enantiomers can give the wanted pharmacological activity, whereas the other one may display inactivity, lower potency, toxicity, and even undesirable side effects. Moreover, in the pharmaceutical industry, the importance of single enantiomer preparation on drug pharmacodynamics or pharmacokinetics is still not completely understood, butin many countries, the regulatory agencies, engaged in the registration of new drugs,focus their efforts inlegislating for the registrationofthe single enantiomers. In this regards, pharmaceutical industries are asked to provide complete information about the stereochemistry and stereoselectivity of all chiral products as well as the stereoselective analytical techniques for their determination. In this context, US Food and Drug Administration and other health regulatory agencies have issued definite guidelines for both the marketing of chiral drugs and their enantiomeric separation [2].

1- Introduction

2- Experimental procedure

3- Result and discussions

4- Conclusions

References

Abstract

This study investigates the simultaneous effect of nano-silica and steel fiber on the fresh and hardened state performance of self-compacting geopolymer concretes (SCGC). For this purpose, self-compacting geopolymer concretes without and with nano-silica (0, 1% and 2%), and without and with steel fiber (0, 0.5% and 1%) were produced. Hooked-end steel fibers were used with a length of 30 mm and an aspect ratio of 40. Self-compacting geopolymer mixes were produced using 50% fly ash (FA) and 50% ground granulated blast furnace slag (GGBFS) with a constant alkaline activator to binder ratio of 0.5. For the alkaline activator, sodium silicate solution (Na2SiO3) and sodium hydroxide solution (NaOH) were utilized with a ratio (Na2SiO3/NaOH) of 2.5. Fresh state experiments were carried out via slump flow, L-Box, and V-funnel tests, while hardened state experiments were conducted using compressive strength, flexural strength, and bonding strength tests to estimate the effects of nano-silica and steel fiber together on the resulting performances of SCGC specimens. Test results were also evaluated statistically in order to clarify the contributions of the important parameters on the resulting performance. Moreover, correlations between the experimental data were studied to investigate the relationships between the fresh and hardened state performances. The results demonstrated that incorporation of nano-silica and steel fiber affected the fresh state properties adversely; however, a combined utilization of them improved bond strength and flexural performance of the SCGC specimens significantly. In addition, the effect of nano-silica was found to be dominant on fresh state properties and compressive strength, while the effect of steel fiber was found to be superior on flexural performance and bonding strength.

Introduction

Concrete is the most commonly used structural material due to the availability of raw materials and ease of shaping. However, significant amount of greenhouse gases (CO2, etc.) are released to the environment due to the combustion of fossil fuels and the decarbonization of limestone during the cement production process. In addition, after aluminum and steel material, ordinary Portland cement (OPC) can be considered as the most energy requiring material [1,2]. Therefore, the negative impacts of CO2 on the environment and the high amount of required energy are significant issues for both cement industry and future of mankind. New enviroment-friendly structural materials should be utilized instead of ordinary concrete to cope with environmental problems [3,4]. Recently, the geopolymer concrete has started to emerge as an environment-friendly concrete as an alternative to ordinary (OPC) concrete [5–7]. Geopolymer concretes have received vast amount of attention due to the significant reduction in both the amount of CO2 release and necessity of natural resources. Unlike to OPC, the manufacture of the raw materials does not require a calcining process leading to reduction in the energy consumption. It is pointed out in literature that amount of CO2 release of the geopolymer concrete is 5–6 times lower as compared to the OPC concrete [8,9]. Furthermore, the usage of geopolymer concrete not only decreases the CO2 emissions considerably, but also uses the byproduct wastes of the alumino-silicate composition to fabricate innovative construction materials [10,11].

1- Introduction

2- Experimental program

3- Experimental procedures

4- Results and discussion

5- Conclusions

References

Abstract

This study investigated the effects of combined utilization of wollastonite particles and recycled waste ceramic aggregate (RWCA) on high strength concrete (HSC) properties. Two groups of mixtures were manufactured: 1) concrete mixtures in which cement was partially replaced with wollastonite at values ranging from 10% to 50%, and 2) mixtures in which wollastonite was used at the aforementioned dosages and 50% of natural coarse aggregate was replaced with RWCA. In addition, 10% of cement weight micro-silica was added to all mixtures. The concrete behavior in terms of strength, durability, resistance against acidic environment, and performance under elevated temperatures ranging from 20 °C to 800 °C was assessed. Furthermore, the effect of wollastonite and RWCA inclusions on the microstructure of samples was studies using scanning electron microscopy (SEM). It was shown that wollastonite has an adverse impact on concrete workability and compressive strength. For example, 34% and 6% reduction in slump and 28-day compressive strength at wollastonite dosage of 50% was observed, respectively. On the other hand, the 28-day splitting tensile strength and flexural strength were respectively increased by 4.25% and 10% at 50% wollastonite content with respect to the control concrete. Furthermore, inclusions of RWCA improved the performance of concrete. For example, the 28-day compressive strength was increased by 24% in mixture with 50% wollastonite content with reference to the control concrete. In addition, the strength retention at 800 °C for mixture with RWCA was 16% higher than that of mixture without RWCA. Thus, it was concluded replacing coarse aggregate with RWCA improves the strength and durability properties of concrete and replacing 30% of cement with wollastonite particles strikes a balance between workability and strength of concrete.

Introduction

Concrete is one the most widely used structural material in construction industries due to the ease of access of its ingredients, high durability, and low maintenance cost. Large volumes of concrete are being manufactured all around the world, which has raised some concerns regarding depletion of natural raw aggregate [1] and greenhouse effects generated by ordinary Portland cement production [2–5]. In this regard, green concrete construction, which is concerned with effective management of different forms of industrial or agricultural wastes through introducing them into concrete has drawn the attention of many researchers. In this regard, a great part of the studies has been dedicated to the utilization of industrial by-products such as ground blast furnace slag [6–9], steel slag [10,11], cement kiln dust [12] and also agricultural by-products including rice husk ash [13], sugarcane bagasse ash [14,15], fly ash [16,17], palm oil fuel ash [18] as replacement of cement or aggregate to manufacture sustainable, green and eco-friendly concrete. Also, other types of materials such as pozzolanic materials [13] and fiber-type materials including metallic fibers [19], polymeric fibers (e.g. nylon and polypropylene) [20], glass fibers [21,22], and natural fibers [23] have been successfully incorporated in concrete production. With the growth in population and subsequent urban developments, ceramic waste is being disposed in large volumes, causing environmental issues in terms of landfilling and waste treatment. The large amount of this waste material has encouraged many researchers to incorporate it in concrete manufacturing [24,25]. Anderson et al. [26] studied the mechanical behavior of concrete containing 20%, 25%, 35%, 50%, 65%, 75%, 80% and 100% ceramic waste used as replacement of coarse aggregate. Rashid et al. [27] conducted an experimental and numerical study on the performance of concrete with ceramic waste aggregate. It was shown that replacing natural aggregate with 30% ceramic waste leads to the highest compressive strength and minimal environmental impact. Martins et al. [28] evaluated the residual strength of concrete containing 20, 50, and 100% recycled ceramic waste subjected to temperatures of 200, 400, and 600
C for 60 min. Significant reduction in strength and also spalling were observed at the highest temperature. In a similar study, Vieira et al.

Nanostructured materials have attracted great interest because of their tunable structures and broad applications [1–5]. Among variable nanostructures, the development of porous nanostructures is an important research area because of their unique physicochemical properties and applicability such as for adsorption, biomedicine, chromatography, catalysis, energy convergence, and gas storage [6–10]. Variable porous nanostructured materials have been applied in catalysis research areas for elevating the efficiency of the catalytic transformations [11–14]. For instance, mesoporous silica and alumina materials have been used as supports for precious nanoparticles (NPs) catalysts due to their low cost, large surface area and porosity, chemical and thermal stability, mechanical strength, and simple synthesis [15–17]. Mesoporous inorganic materials that supported palladium NPs catalysts have expedited various important reactions [18–20]. Another interesting feature of mesoporous silica is the multitude of possible modifications that can be used for easy organics functionalization to present the desired properties [21, 22]. Mesoporous silica materials functionalized with acidic groups (e.g., –COOH, – SO3H, –SH) and/or basic groups (e.g., –NH2, –NRH, –NR2) have been utilized as non-metallic solid catalysts in various reactions such as cascade reactions [23–25]. These heterogeneous catalysts have the benefits of simple recovery and reuse after the accomplishment of reactions and present green chemical processes in comparison to their homogeneous counterparts [26–28]. Although great efforts have been achieved to develop highly stable and sustainable solid acid/base catalysts, there are still major deficiencies with most matrixes needing rectification including available active catalytic sites, catalytic efficiency, and substrates diffusion [29, 30]. In addition, reactants adsorption and interaction with the functional groups in small pore-size supports restrict the effectiveness of these heterogeneous catalysts [31].