A sulfobetaine zwitterionic polymer-drug conjugate for multivalent paclitaxel and gemcitabine co-delivery.

A zwitterionic polymer-drug conjugate (ZPDC) strategy is developed for the co-delivery of paclitaxel (PTX) and gemcitabine (GEM) chemotherapeutics, as well as a near-infrared fluorescence imaging agent cyanine5.5 (Cy5.5). The well-defined ZPDC is synthesized by tandem azide-alkyne and thiol-ene click functionalization of a biodegradable acetylenyl/allyl-functionalized polylactide and zwitterionic character is conferred by sulfobetaine. It has a number-average molecular weight of 53.6 kDa, comprising 6.5% PTX and 17.7% GEM by weight. Cy5.5 moieties are readily introduced to the ZPDC via conjugation. In aqueous solutions, the ZPDC exhibits a hydrodynamic diameter of 46 nm. In vitro MIA PaCa-2 human pancreatic cancer cells show strong ZPDC cellular uptake and cytotoxicity. In mice, the ZPDC exhibits long blood circulation, effective tumor accumulation, biocompatibility, therapeutic effect, and integrated imaging capacity. Overall, this work illustrates that ZPDCs are promising systems for chemotherapy delivery and bioimaging applications.

A multifunctional biodegradable brush polymer-drug conjugate for paclitaxel/gemcitabine co-delivery and tumor imaging.

A multifunctional biodegradable brush polymer-drug conjugate (BPDC) is developed for the co-delivery of hydrophobic paclitaxel (PTX) and hydrophilic gemcitabine (GEM) chemotherapeutics, as well as a tumor imaging agent. A novel ternary copolymer of conventional, acetylenyl-functionalized and allyl-functionalized lactides is prepared to serve as the backbone precursor of BPDC. Acetylenyl groups of the copolymer are then reacted with poly(ethylene glycol) (PEG) side chains and cyanine5.5, a fluorescent probe, via azide-alkyne click reactions. Subsequently, the allyl groups of the yielded PEG-grafted brush polymer are used to covalently link PTX and GEM onto the backbone via thiol-ene click reactions. The resulting BPDC exhibits an average hydrodynamic diameter of 111 nm. Sustained and simultaneous release of PTX and GEM from the BPDC is observed in phosphate buffered saline, with the release of PTX showing sensitivity in mild acidic conditions. In vitro studies using MIA PaCa-2 human pancreatic cancer cells illustrate the cellular uptake and cytotoxicity of the BPDC. In vivo, the BPDC possesses long blood circulation, tumor accumulation, and enables optical tumor imaging. Further development and testing is warranted for multifunctional conjugated brush polymer systems that integrate combination chemotherapies and imaging.

Ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction for the simultaneous determination of 12 new antidepressants and 2 antipsychotics in whole blood by gas chromatography-mass spectrometry.

Antidepressant drugs are widely used in the treatment of different psychiatric disorders, as well as in conjunction with antipsychotics for the treatment of major depressive disorder. In this study, a simple and rapid ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME) method was developed for the simultaneous determination of 12 new antidepressants (norfluoxetine, fluoxetine, fluvoxamine, agomelatine, mirtazapine, moclobemide, melitracen, N-desmethylmirtazapine, maprotiline, sertraline, citalopram, paroxetine) and 2 antipsychotics (clozapine and haloperidol) in human whole blood by gas chromatography-mass spectrometry (GC-MS). Different parameters affecting the UA-LDS-DLLME were optimized and the optimal conditions were as follows: 100µL of toluene as extraction solvent, extraction pH 12 and 3min of ultrasound stirring. Good linearity (R2≥0.991) was obtained at the concentration range of 15-1500ng/mL for norfluoxetine, fluoxetine, fluvoxamine, melitracen, maprotiline and citalopram, and 5-500ng/mL for agomelatine, mirtazapine, moclobemide, N-desmethylmirtazapine, sertraline, paroxetine, clozapine and haloperidol. The intra-day and inter-day precision were all less than 10%, and accuracy of intra-day and inter-day were in the range of -12.7% to 7.9% and -13.9 to 11.8%, respectively. The extraction recoveries of most analytes were more than 60%. The UA-LDS-DLLME/GC-MS method was demonstrated with acceptable precision, accuracy and good specificity for the simultaneous determination of 12 antidepressants and 2 antipsychotics, and has been successfully applied in a real case.

Development of a field sampling method based on magnetic nanoparticles for the enrichment of pesticides in aqueous samples.

A field sampling method based on magnetic core-shell silica nanoparticles was developed for field sampling and the enrichment of low concentrations of pesticides in aqueous samples. The magnetic nanoparticles could be easily extracted from water samples by a custom-made magnetic nanoparticle collector. The recovery of 15 mg of magnetic particles from a 500 mL water sample was 90.8%. Mixtures of seven pesticides spiked into pure water and pond water were used as marker samples to evaluate the field sampling method. The average recoveries at three levels of spiking were in the range 60.0-104.7% with relative standard deviations <7.1%. The proposed method has good linearity with a correlation coefficient >0.9990 in the concentration range 0.5-15 µg L(-1). The results of the analysis of a sample of poisoned pond water indicate that this method is fast, convenient and efficient for the field sampling and enrichment of pesticides in aqueous samples.

Solid-phase extraction based on magnetic core-shell silica nanoparticles coupled with gas chromatography-mass spectrometry for the determination of low concentration pesticides in aqueous samples.

A simple and effective preconcentration method based on magnetic core-shell silica nanoparticles with C(18)-modified surface was developed for the analysis of pesticide residues in environmental water samples by gas chromatography-mass spectrometry. Several kinds of organophosphorous and pyrethroid pesticides including methamidophos, dichlorvos, orthene, phorate, dimethoate, carbofuran, bifenthrin, fenpropathrin, cypermethrin, fenvalerate, and deltamethrin were used as model compounds to systematically evaluate the method. Various parameters, including the amounts of magnetic nanoparticles absorbents, extraction time, eluting solvent, eluting volume, and sample pH values were optimized. The optimized method affords low detection limits (signal-to-noise ratio = 3) from 0.001 to 0.008 µg/L, and shows good linearity with correlation coefficients over 0.9990 in the concentration range of 0.025-0.5 µg/L. Average recoveries at three spiked levels were in the range of 70.2-110.2% with relative standard deviations below 9.6%. A maximum enrichment factor of 1015 times was achieved. Analysis results of poisoned pond water indicate that this method is fast, convenient, and efficient for the detections of low-concentration pesticides in aqueous samples.

Anticancer constituents and cytotoxic activity of methanol-water extract of Polygonum bistorta L.

This study was specifically designed to identify anticancer constituents in methanol-water extract of Polygonum bistorta L. and evaluate its cytotoxicity. For this purpose methanol-water (40:60 v/v) extract was subjected to conventional preparative high pressure liquid chromatography and 13 fractions were obtained. Constituents of obtained fractions were separated and identified with the help of GC-MS and LC-DAD-ESI-MS. Anticancer phenolic compounds such as gallic acid, protocatechuic acid, p-hydroxybenzoic acid, chlorogenic acid, vanillic acid, syringic acid, catechol, 4-methyl catechol, syringol and pyrogallol and fatty acids such as linoleic acid, myristic acid and palmitic acid were separated from different fractions. Fractions were evaluated for their cytotoxic activity on a rarely studied human hepatocellular carcinoma cell line (HCCLM3). 11 fractions showed good to strong cytotoxicity in a range of 200 µg/mL-800 µg/mL, whereas 2 fractions did not show any activity even at 800 µg/mL and no anticancer constituent was detected from them. 50 percent growth inhibition (GI50) values for five most active fractions were calculated and results were in a range of 86.5 (±3) µg/mL-126.8 (±3) µg/mL. 3 out of these 5 most active fractions were found to contain phenolic content in them whereas all other fractions containing phenolic content did possess cytotoxic activity that may suggest the importance of phenolic constituents in anticancer activity. Moreover, the results also showed a definite dose dependent relationship between amount of fractions and cytotoxic activity.