New synthetic adriamycin-incorporated chitosan nanoparticles with enhanced antioxidant, antitumor activities and pH-sensitive drug release.

In this paper, adriamycin-incorporated chitosan nanoparticles were synthesized by ionic gelation using negatively charged carboxymethyl chitosan and positively charged 2-hydroxypropyltrimethyl ammonium chloride chitosan. The method was efficient to obtain nanoparticles with low polydispersity index and small hydrodynamic diameter. And high zeta potential value indicated that nanoparticles had good stability. The adriamycin release of nanoparticles represented a significant response to pH, with the fastest release in phosphate buffer solution at pH 6.8. Meanwhile, the antioxidant efficiency of nanoparticles was assayed, and nanoparticles represented significant enhancement in radicals scavenging activity. The assay of cell viability by CCK-8 test exhibited that nanoparticles led to statistically significant decrease in cell viability for four kinds of cancer cells (HEPG-2, A549, MCF-7, and BGC-823). It was indicated that the nanoparticles with enhanced biological activity, reduced cytotoxicity, and pH-sensitive release could be served as potential drug carrier in drug delivery system.

LC-MS/MS quantification of ataluren and ataluren acyl glucuronide in human plasma/urine: application in clinical studies.

Background: This paper describes for the first-time analytical procedures established to resolve the challenges associated with simultaneous and direct quantification of ataluren and ataluren-O-1ß-acyl glucuronide (AAG) by LC-MS/MS in human plasma and urine matrices. Methodology/results: The plasma quantification method was validated for calibration range of 12.5-12500 ng/ml for ataluren and 6.25-2500 ng/ml for AAG. The urine quantification method was validated for calibration range of 0.01-10 and 1-1000 µg/ml for ataluren and AAG, respectively. Plasma and urine samples were stabilized upon collection and through storage to prevent hydrolysis and acyl migration of AAG. Conclusion: Methods described in this paper enabled successful completion of ataluren clinical pharmacology studies for simultaneous pharmacokinetic assessment of ataluren and AAG.

Determination of chitosan content with ratio coefficient method and HPLC.

The determination of chitosan is a significant topic that has been growing in importance for a variety of fields. To quantify chitosan, various analytical methods can be used. When high performance liquid chromatographic (HPLC) is used for quantitative analysis of chitosan, the chitosan is mainly hydrolyzed into glucosamine salts, which are determined by HPLC. Average deacetylation degree (DD) has an effect on acid hydrolysis of chitosan. In this paper, chitosan with different average DDs was hydrolyzed to observe its effect on the determination of chitosan content, and that the study of combining acid hydrolysis rates of chitosan (α) with different average DDs and chitin (ß) standard to form ratio coefficients (γ) to quantify chitosan was designed. Then, the table about γ values within certain average DD ranges of chitosan was obtained. By using γ and α, the actual content of chitosan could be obtained simply and accurately.

Promoted liquid-phase hydrodechlorination of chlorophenol over Raney Ni via controlling base: Performance, mechanism, and application.

The potential effect of base on Raney Ni-catalyzed hydrodechlorination (HDC) of chlorophenol was studied. Compared to weak inorganic bases, strong inorganic bases (NaOH and KOH) and triethylamine (Et3N) were more favorable to promote Raney Ni-catalyzed HDC reaction. Moreover, a stoichiometric amount of NaOH/Et3N was found to be optimal for the HDC reaction, and up to 100% conversion of 4-chlorophenol was achieved within 30 min. Catalyst characterization (SEM, EDXS, and XRD) combined with ICP-OES analysis were introduced to better understand the mechanism for the promoted effect of base on the HDC reaction. The results showed that the optimal amount of strong inorganic bases and Et3N efficiently eliminated HCl corrosion to Raney Ni, greatly reduced the active phase Ni and Al leaching, and avoided collapse of the catalyst framework. Based on the mechanism, the best bases and their optimal amount were developed for further disposal of polychlorinated phenols, and excellently stepwise HDC of polychlorinated phenols was achieved. Recycling tests showed that Raney Ni could be reused at least 5 times for the HDC reaction with the stoichiometric amount of NaOH, which was a promising option for the HDC of wastewater containing chlorophenols over Raney Ni.

Quantitation of cytidine-5'-monophospho-N-acetylneuraminic acid in human leukocytes using LC-MS/MS: method development and validation.

The biosynthesis of sialic acid (Neu5Ac) leads to the intracellular production of cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac), the active sialic acid donor to nascent glycans (glycoproteins and glycolipids) in the Golgi. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase myopathy is a rare autosomal recessive muscular disease characterized by progressive muscle weakness and atrophy. To quantify the intracellular levels of CMP-Neu5Ac as well as N-acetylmannosamine (ManNAc) and Neu5Ac in human leukocytes, we developed and validated robust liquid chromatography-tandem mass spectrometry methods. A fit-for-purpose approach was implemented for method validation. Hydrophilic interaction chromatography was used to retain three hydrophilic analytes. The human leukocyte pellets were lysed and extracted in a methanol-water mixture and the leukocyte extract was used for LC-MS/MS analysis. The lower limits of quantitation for ManNAc, Neu5Ac and CMP-Neu5Ac were 25.0, 25.0 and 10.0 ng/ml, respectively. These validated methods were applied to a clinical study.

Preparation of starch derivatives bearing urea groups and the evaluation of antioxidant, antifungal, and antibacterial activities.

Several starch derivatives bearing urea groups (TUCAST, MTUCAST, and PTUCAST) based on 6-O-chloroacetylated starch (CAST) were successfully designed and synthesized. FT-IR, 1H NMR spectroscopy, and elemental analysis were carried out to identify the structural characteristics of starch derivatives. The antioxidant activity of starch derivatives was tested by superoxide-radical scavenging and hydroxyl-radical scavenging assays. Their antifungal activity against Fusarium oxysporum f. sp. cucumebrium Owen, Phomopsis asparagus, and Fusarium oxysporum f. sp. niveum was estimated by hyphal measurement. Furthermore, the antibacterial activity against Escherichia coli and Staphylococcus aureus was evaluated by optical density method. Compared to starch, the products bearing urea groups showed enhanced antifungal action as well as an excellent antioxidant and antibacterial activities. Their bioactivities decreased roughly in the order of PTUCAST > MTUCAST > TUCAST > CAST > starch, which matched with the electron-withdrawing property of the different substituted groups of urea. Besides, the cytotoxic activity of starch and synthesized derivatives against L929 cells was evaluated using CCK-8 assay in vitro and all samples showed weak cytotoxicity. The results suggested that these novel starch derivatives possessing satisfactory bioactivities could be widely used in the food industry.

Synthesis of Novel Chitin Derivatives Bearing Amino Groups and Evaluation of Their Antifungal Activity.

Chemical modification is one of the most effective methods to improve the biological activity of chitin. In the current study, we modified C3-OH and C6-OH of chitin (CT) and successfully synthesized 6-amino-chitin (NCT) and 3,6-diamino-chitin (DNCT) through a series of chemical reactions. The structure of NCT and DNCT were characterized by elemental analyses, FT-IR, 13C NMR, XRD, and SEM. The inhibitory effects of CT, NCT, and DNCT against six kinds of phytopathogen (F. oxysporum f. sp. cucumerium, B. cinerea, C. lagenarium, P. asparagi, F. oxysporum f. niveum, and G. zeae) were evaluated using disk diffusion method in vitro. Meanwhile, carbendazim and amphotericin B were used as positive controls. Results revealed that 6-amino-chitin (NCT) and 3,6-diamino-chitin (DNCT) showed improved antifungal properties compared with pristine chitin. Moreover, DNCT exhibited the better antifungal property than NCT. Especially, while the inhibition zone diameters of NCT are ranged from 11.2 to 16.3 mm, DNCT are about 11.4⁻20.4 mm. These data demonstrated that the introduction of amino group into chitin derivatives could be key to increasing the antifungal activity of such compounds, and the greater the number of amino groups in the chitin derivatives, the better their antifungal activity was.

Synthesis, Characterization, and Antifungal Activity of Pyridine-Based Triple Quaternized Chitosan Derivatives.

In this study, a series of triple quaternized chitosan derivatives, including 6-O-[(2-hydroxy-3-trimethylammonium)propyl]-2-N-(1-pyridylmethyl-2-ylmethyl)-N,N-dimethyl chitosan chloride (7), 6-O-[(2-hydroxy-3-trimethylammonium)propyl]-2-N-(1-pyridylmethyl-3-yl- methyl)-N,N-dimethyl chitosan chloride (8), and 6-O-[(2-hydroxy-3-trimethylammonium)propyl]- 2-N-(1-pyridylmethyl-4-ylmethyl)-N,N-dimethyl chitosan chloride (9) were successfully designed and synthesized via reacting epoxypropyl trimethylammonium chloride with the N-pyridinium double quaternized chitosan derivatives. Detailed structural characterization was carried out using FT-IR and ¹H-NMR spectroscopy, and elemental analysis. Besides, the activity of the triple quaternized chitosan derivatives against three common plant pathogenic fungi, Watermelon fusarium, Fusarium oxysporum, and Phomopsis asparagi, was investigated in vitro. The results indicated that the triple quaternized chitosan derivatives had enhanced antifungal activity when compared to double quaternized chitosan derivatives and chitosan, especially at 1.0 mg/mL, which confirmed the theory that the higher density of positive charge contributed to the antifungal activity. Moreover, 8 with an almost 99% inhibitory index showed the better antifungal activity against Watermelon fusarium. Moreover, the cytotoxicity of the products was also evaluated in vitro on 3T3-L1 cells and all the triple quaternized chitosan derivatives exhibited low cytotoxicity. These results suggested that triple quaternized chitosan derivatives may be used as good antifungal biomaterials.

Validation of an LC-MS/MS method for simultaneous quantification of venlafaxine and its five metabolites in rat plasma and its application in a pharmacokinetic study.

A sensitive, selective, and reliable LC-MS/MS method was developed and validated for simultaneous quantification of venlafaxine (VEN) and its 5 metabolites (ODV, NDV, NNDDV, OHV and NODDV) in rat plasma. The calibration ranges are 15.0 to 6000 ng/mL for VEN, 1.00 to 400 ng/mL for ODV, 5.00 to 2000 ng/mL for NDV, 1.00 to 400 ng/mL for NNDDV, 10.0 to 4000 ng/mL for OHV, and 0.200 to 20.0 ng/mL for NODDV. Briefly, 50 µL of rat plasma was extracted using liquid-liquid extraction (LLE) with methyl tert-butyl ether (MTBE). The analytes were separated on an Agilent SB-Phenyl (50 mm × 4.6 mm, 3.5 µm) column using a binary gradient of 0.1% formic acid in water versus 0.1% formic acid in acetonitrile at a flow rate of 0.8 mL/min. The method was validated following FDA guidance for bioanalytical method validation. Validated method was successfully applied to a pharmacokinetic study of VEN orally administered to rats.

Synthesis of inulin derivatives with quaternary phosphonium salts and their antifungal activity.

Inulin is a kind of renewable and biodegradable carbohydrate with good water solubility and numerous physiological functions. For further utilization of inulin, chemical modification can be applied to improve its bioactivities. In this paper, five novel inulin derivatives were synthesized via chemical modification with quaternary phosphonium salt. Their antifungal activity against three kinds of plant pathogens including Colletotrichum lagenarium, Phomopsis asparagi, and Fusarium oxysporum was assessed with radial growth assay in vitro. Results revealed that all the inulin derivatives exhibited improved antifungal activity compared with inulin. Particularly, inulin modified with triphenylphosphine (TPhPAIL) exhibited the best antifungal activity with inhibitory indices of 80.0%, 78.8%, and 87.4% against Colletotrichum lagenarium, Phomopsis asparagi, and Fusarium oxysporum at 1.0mg/mL respectively. The results clearly showed that chemical modification of inulin with quaternary phosphonium salt could efficiently improve derivatives' antifungal activity. Further analysis of results indicated that the antifungal activity was influenced by alkyl chain length or electron-withdrawing ability of the grafted quaternary phosphonium salts. Longer alkyl chain lengths or the stronger electron-withdrawing groups would lead to enhanced antifungal efficacy.

Novel Water Soluble Chitosan Derivatives with 1,2,3-Triazolium and Their Free Radical-Scavenging Activity.

Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed for its potential of providing high bioactivity and good water solubility. A new class of chitosan derivatives possessing 1,2,3-triazolium charged units by associating "click reaction" with efficient 1,2,3-triazole quaternization were designed and synthesized. Their free radical-scavenging activity against three free radicals was tested. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that triazole or triazolium groups enable the synthesized chitosan to possess obviously better radical-scavenging activity. Moreover, the scavenging activity against superoxide radical of chitosan derivatives with triazolium (IC50 < 0.01 mg mL-1) was more efficient than that of derivatives with triazole and Vitamin C. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging assay, the same pattern were observed, which should be related to the triazolium grafted at the periphery of molecular chains.

The evaluation of antioxidant and antifungal properties of 6-amino-6-deoxychitosan in vitro.

We synthesized 6-amino-6-deoxychitosan (NCS) through a series of reactions from chitosan (CS). The antioxidant ability of CS and NCS were investigated in vitro, including that of DPPH-radical and hydrogen peroxide, reducing power, chelating abilities and inhibition of lipid peroxidation. As expected, after the introduction of amino groups, antioxidant ability had improved significantly. Especially, scavenging effect against DPPH-radical and hydrogen peroxide of NCS were 97% and 92% at 1.6mg/mL, respectively. Moreover, inhibition of lipid peroxidation was 57% at 0.1mg/mL. And the reducing power of NCS was 0.68 at 0.8mg/mL. Meanwhile, inhibitory effects against four fungi were also tested. Antifungal activity of NCS were better than those of CS and antifungal activity had improved more than 20% at 0.5mg/mL against these four kinds of plant pathogens. Based on the above results, it was reasonable to speculate that the obtained antioxidant ability and antifungal activity of NCS might benefit from amino groups on chitosan backbone. These in vitro results suggest the possibility that NCS as antioxidant compound could be effectively alleviate oxidative stress and thus inhibit the oxidative mechanisms that lead to degenerative diseases.

Novel Amino-Pyridine Functionalized Chitosan Quaternary Ammonium Derivatives: Design, Synthesis, and Antioxidant Activity.

Chemical modification of chitosan is increasingly studied for its potential of providing new applications of chitosan. Here, a group of novel chitosan quaternary ammonium derivatives containing pyridine or amino-pyridine were designed and successfully synthesized through chemical modification of chitosan. Pyridine and amino-pyridine were used as functional groups to improve the antifungal activity of chitosan derivatives. The chitosan derivatives' antioxidant activity against hydroxyl-radical and 1,1-Diphenyl-2-picrylhydrazyl (DPPH)-radical was tested in vitro. The results showed that chitosan derivatives had better water solubility and stronger antioxidant activity compared with chitosan in all assays. Especially, compounds 3C and 3E (with 3-amino pyridine and 2,3-diamino pyridine as substitute respectively) exhibited stronger hydroxyl-radical and DPPH-radical scavenging ability than other synthesized compounds. These data demonstrated that the synergistic effect of the amino group and pyridine would improve the antioxidant activity of chitosan derivatives, and the position of the amino group on pyridine could influence the antioxidant property of chitosan derivatives.

Synthesis of water soluble chitosan derivatives with halogeno-1,2,3-triazole and their antifungal activity.

Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed prior to further utilization. Three novel water soluble chitosan derivatives containing 1,2,3- triazole with or without halogen was designed and synthesized. Their antifungal activity against three kinds of phytopathogens was estimated by hyphal measurement in vitro. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that thiazolyl groups enable the synthesized chitosan to possess obviously better antifungal activity. Moreover, CTCTS and BTCTS, which have halogens at the periphery of polymers, inhibited the growth of tested phytopathogens more effectively with inhibitory indices of 81-93% at 1.0mg/mL. The halogens could have a synergistic effect with triazole as they exhibited antifungal activity and electron-withdrawing capacity, which improve the antifungal activity of chitosan derivatives.

Global Exponential Stability of Almost Periodic Solution for Neutral-Type Cohen-Grossberg Shunting Inhibitory Cellular Neural Networks with Distributed Delays and Impulses.

A kind of neutral-type Cohen-Grossberg shunting inhibitory cellular neural networks with distributed delays and impulses is considered. Firstly, by using the theory of impulsive differential equations and the contracting mapping principle, the existence and uniqueness of the almost periodic solution for the above system are obtained. Secondly, by constructing a suitable Lyapunov functional, the global exponential stability of the unique almost periodic solution is also investigated. The work in this paper improves and extends some results in recent years. As an application, an example and numerical simulations are presented to demonstrate the feasibility and effectiveness of the main results.

Comparative study on catalytic hydrodehalogenation of halogenated aromatic compounds over Pd/C and Raney Ni catalysts.

Catalytic hydrodehalogenation (HDH) has proved to be an efficient approach to dispose halogenated aromatic compounds (HACs). Liquid-phase HDH of single and mixed halobenzenes/4-halophenols with H2 over 5% Pd/C and Raney Ni catalyst are investigated and compared. For liquid-phase HDH of single HACs, hydrogenolytic scission reactivity of C-X bonds decreases in order of C-Br > C-Cl > C-I > C-F over Pd/C catalyst, and in order of C-I > C-Br > C-Cl > C-F over Raney Ni catalyst. To clarify the reason why hydrogenolytic scission reactivity of C-X bonds over Pd/C and Raney Ni catalysts exhibits different trends, liquid-phase HDH of mixed HACs over Pd/C and Raney Ni catalysts were studied, and catalysts are characterized by SEM, EDX, and XRD techniques. It was found that the high adsorption of iodoarenes on Pd/C catalyst caused the HDH reactivity of iodoarenes to be lower than that of chloroarenes and bromoarenes in the HDH of single HACs. Moreover, the adsorption of in situ produced iodine ion (I(-)) to catalyst surface would result in the decline of catalytic activity, which might be the main reason why the HDH reactivity of HACs in the presence of NaI is rather low.

Novel triazolyl-functionalized chitosan derivatives with different chain lengths of aliphatic alcohol substituent: Design, synthesis, and antifungal activity.

Chemical modification of chitosan is increasingly studied for its potential of providing new application for chitosan. Here, we modify chitosan at its primary hydroxyl via 'click chemistry', and a group of novel water soluble chitosan derivatives with substituted 1,2,3-triazolyl group were designed and synthesized. Aliphatic alcohols with different lengths were used as functional dendrons to improve the antifungal activity of chitosan derivatives. Meanwhile, their antifungal activity against two kinds of phytopathogens was estimated by hypha measurement in vitro. All the chitosan derivatives exhibited excellent activity against tested fungi. It is found that the antifungal activity of chitosan derivatives against the tested fungi increases with augment in the chain length of straight aliphatic alcohols. And the hydrophobic moiety (alkyl) at the periphery of the synthesized chitosan derivatives tends to affect their antifungal activity.

Extraction, degree of polymerization determination and prebiotic effect evaluation of inulin from Jerusalem artichoke.

The tubers of Jerusalem artichoke are rich of inulin, which makes the plant one of primary inulin resources in China. The aim of this study was to extract inulin from tubers and test the degree of polymerization (DP) 10 days before flowering to 80 days after flowering. The DP of inulin reaches a maximum of 19 at 50 days after flowering. The variation tendencies of inulin content and DP were almost the same, which increase rapidly at the beginning and then decrease gradually at a lower speed. Meanwhile, the effects of inulin on probiotics in yogurt have been evaluated. It indicated that inulin with low DP has higher activities. Experimental data improve the understanding of status change of inulin in whole growth of Jerusalem artichoke tubers in Northeastern China and are instructive to get inulin with different properties.

Synthesis of amphiphilic aminated inulin via 'click chemistry' and evaluation for its antibacterial activity.

Inulins are a group of abundant, water-soluble, renewable polysaccharides, which exhibit attractive bioactivities and natural properties. Improvement such as chemical modification of inulin is often performed prior to further utilization. We hereby presented a method to modify inulin at its primary hydroxyls to synthesize amphiphilic aminated inulin via 'click chemistry' to facilitate its chemical manipulation. Additionally, its antibacterial property against Staphylococcus aureus (S. aureus) was also evaluated and the best inhibitory index against S. aureus was 58% at 1mg/mL. As the amphiphilic aminated inulin is easy to prepare and exhibits improved bioactivity, this material may represent as an attractive new platform for chemical modifications of inulin.

Synthesis and antifungal activity of thiadiazole-functionalized chitosan derivatives.

A groups of novel water soluble chitosan derivatives containing 1,3,4-thiadiazole group were synthesized including 1,3,4-thiadiazole (TPCTS), 2-methyl-1,3,4-thiadiazole (MTPCTS), and 2-phenyl-1,3,4-thiadiazole (PTPCTS). Their antifungal activity against three kinds of phytopathogens was estimated by hypha measurement in vitro, and the fungicidal assessment shows that the synthesized chitosan derivatives have excellent activity against tested fungi. Of all the synthesized chitosan derivatives, MTPCTS inhibited the growth of the tested phytopathogens most effectively with inhibitory indices of 75.3%, 82.5%, and 65.8% against Colletotrichum lagenarium (Pass) Ell.et halst, Phomopsis asparagi (Sacc.) Bubak, and Monilinia fructicola (Wint.) Honey respectively at 1.0 mg/mL. These indices are higher than those of chitosan. These data also demonstrate that the hydrophobic moiety (alkyl and phenyl) and the length of alkyl substituent in thiadiazole tend to affect the antifungal activity of chitosan derivatives. It is hypothesized that thiadiazole groups enable the synthesized chitosan to possess obviously better antifungal activity and good solubility in water.