Eu3+ functionalized Sc-MOFs: Turn-on fluorescent switch for ppb-level biomarker of plastic pollutant polystyrene in serum and urine and on-site detection by smartphone.

The harm of plastic pollutants for human and environment is being paid more and more attention. Polystyrene (PS) and styrene are toxic compounds used in large quantities in the production of fiberglass reinforced polyesters. In this work, a simple method was designed for independent detecting polystyrene and styrene biomarker (phenylglyoxylic acid, PGA) in serum and urine. We prepared Eu3+ functionalized Sc-based metal-organic frameworks as turn-on fluorescent switch for PGA. The distinct enhanced luminescence is observed from the Eu@MOFs with addition of PGA. The fabricated fluorescent switch has several appealing features including high sensitivity (LOD = 4.16 ppb), quick response time (less than 5s) and broad linear range (0.02mg/mL to 0.5mg/mL). Furthermore, Eu@MOFs exhibits excellent selectivity that it is not affected by congeneric biomarkers. More interestingly, a paper-based probe has been devised. The paper-based fluorescence probe would perform an obvious fluorescence change from navy to red with the variety of PGA content. The practicability of the on-site detection platform for quantitative analysis using a colour scanning APP in smartphone has been also demonstrated by coupled with our proposed paper based fluorescence probe. This work first provides a fast, accurate and sensitive method for independent monitoring PS biomarker PGA, and the paper-based probe exhibit a new idea for design portable and easy to operate sensing devices combine with smartphone.

CO2 Biofixation of Actinobacillus succinogenes Through Novel Amine-Functionalized Polystyrene Microsphere Materials.

CO2-derived succinate production was enhanced by Actinobacillus succinogenes through polystyrene (PSt) microsphere materials for CO2 adsorption in bioreactor, and the adhesion forces between A. succinogenes bacteria and PSt materials were characterized. Synthesized uniformly sized and highly cross-linked PSt microspheres had high specific surface areas. After modification with amine functional groups, the novel amine-functionalized PSt microspheres exhibited a high adsorption capacity of 25.3 mg CO2/g materials. After addition with the functionalized microspheres into the culture broth, CO2 supply to the cells increased. Succinate production by A. succinogenes can be enhanced from 29.6 to 48.1 g L-1. Moreover, the characterization of interaction forces between A. succinogenes cells and the microspheres indicated that the maximal adhesive force was about 250 pN. The amine-functionalized PSt microspheres can adsorb a large amount of CO2 and be employed for A. succinogenes anaerobic cultivation in bioreactor for high-efficiency production of CO2-derived succinate.

Micro-impedance cytometry for detection and analysis of micron-sized particles and bacteria.

The sensitivity of a microfluidic impedance flow cytometer is governed by the dimensions of the sample analysis volume. A small volume gives a high sensitivity, but this can lead to practical problems including fabrication and clogging of the device. We describe a microfluidic impedance cytometer which uses an insulating fluid to hydrodynamically focus a sample stream of particles suspended in electrolyte, through a large sensing volume. The detection region consists of two pairs of electrodes fabricated within a channel 200 µm wide and 30 µm high. The focussing technique increases the sensitivity of the system without reducing the dimensions of the microfluidic channel. We demonstrate detection and discrimination of 1 µm and 2 µm diameter polystyrene beads and also Escherichia coli. Impedance data from single particles are correlated with fluorescence emission measured simultaneously. Data are also compared with conventional flow cytometry and dynamic light scattering: the coefficient of variation (CV) of size is found to be comparable between the systems.

In vivo evaluation of the release of zidovudine and polystyrene sulfonate from a dual intravaginal bioadhesive polymeric device in the pig model.

This study focused on determining the concentration of zidovudine (AZT) and polystyrene sulfonate (PSS) in the plasma and vaginal tissue of the large white pig from an intravaginal bioadhesive polymeric device (IBPD). Biocompatible polymers were compressed with AZT and PSS into caplet-shaped devices for insertion into the posterior fornix of the pig vagina. A total of 25 pigs were used in this study. Plasma was sampled from the jugular vein at various time points after insertion of the IBPD reaching 28 days. At day 28, the pigs were euthanized and vaginal tissue was removed and digested with subtilisin for AZT and PSS extraction. The mean concentration detected in vaginal tissue at day 28 was 1.214 ± 0.062 mg/mL for AZT and 1.400 ± 0.071 mg/mL for PSS. Plasma concentration was significantly lower for AZT (0.332 ± 0.014 mg/mL) and PSS (0.256 ± 0.013 mg/mL). This indicated higher retention of AZT and PSS within the vaginal tissue. Molecular mechanics simulations blueprinted polymer-drug-mucin force-field interactions and energies that explicated the spatial preference of AZT and PSS for the vaginal tissue. Histopathotoxicity studies revealed negative-to-mild foreign body events and results strongly suggest that the IBPD may be suitable for prolonged intravaginal drug delivery in preventing the transmission of sexually transmitted infections and HIV/AIDS.

Quantification of extrapulmonary translocation of intratracheal-instilled particles in vivo in rats: effect of lipopolysaccharide.

Particulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. However, important uncertainties remain in the quantification of extrapulmonary translocation of ultrafine particles into blood circulation. Therefore, the widely used radioiodinated technique was applied to radiolabel polystyrene particles with an average diameter of 56.4 and 202 nm, respectively. The extrapulmonary distribution of these particles (3.7 x 10(5) Bq/rat) was quantified at 0.5, 2, 24 and 120 h after intratracheal instillation in rats. Moreover, we have taken into account the possible involvement of pulmonary inflammation in this process. Rats which received a single intratracheal instillation of free 125I or a single intravenous injection of labeled ultrafine particles served as control. The results indicated that the pulmonary deposition of radioactivity was almost unchanged for both sizes. Only small amounts of radioactivity (1.64-2.49%) were recovered in blood shortly after administration of both types of particle, in healthy rats. However, the extent of particle translocation into the blood of the ultrafine size following the pretreatment with lipopolysaccharides was significantly higher (from 1.96 +/- 0.67 to 4.73 +/- 0.31%) compared to larger particles (from 2.19 +/- 0.77 to 2.21 +/- 0.64%). In conclusion, our findings suggest that only a small fraction of intratracheal-instilled ultrafine particles can pass rapidly into systemic circulation, but this translocation is markedly increased following LPS pretreatment. Thus, pulmonary inflammation seems to play a major role in enhancing the extrapulmonary translocation of particles.

Major determinants in hepatic disposition of polystyrene nanospheres: implication for rational design of particulate drug carriers.

The clearance of colloidal particles from the blood circulation occurs by phagocytes and/or endothelial cells, mainly in the liver, the spleen, and the bone marrow. The relative distribution of the injected particles in these organs is known to depend on various factors such as the size and surface properties of the particles and the type of serum proteins adsorbed onto the surface of particles. The basic principles behind their distribution characteristics into the reticuloendothelial system, however, remain unclear. This article reviews major determinants in hepatic disposition of polystyrene nanospheres, especially the relationship among physicochemical properties of the particle surface, the type of blood components associated onto the surface of particles, and their in vivo disposition characteristics in rats, and considerations to be given and implication for the rational design of particulate drug carriers are discussed.

Surface hydrophobicity of particles is not necessarily the most important determinant in their in vivo disposition after intravenous administration in rats.

The in vivo disposition of polystyrene microsphere (MS) with the particle size of 50 nm (MS-50) and lecithin-coated MS-50 (LMS-50) after intravenous administration to rats was characterized. While a rapid elimination from the systemic circulation was observed for MS-50, much more prolonged circulating property was observed for LMS-50. In addition, this in vivo disposition property of LMS-50 was suggested to be ascribed to its lower affinity to the liver, which is the determining organ of the in vivo disposition of MS-50. The evaluation of surface hydrophobicity of MS-50 and LMS-50 in buffer solution revealed that the surface of MS-50 is more hydrophobic than that of LMS-50. However, LMS-50 was oppositely found to be more hydrophobic than that of MS-50 in rat serum. The profiles of serum proteins associated with MS-50 and LMS-50 were also examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results showed that the amounts of some adsorbed proteins are greatly different between MS-50 and LMS-50. From these findings, it was suggested that the substantial difference in the in vivo disposition between MS-50 and LMS-50 would not be attributed to the difference in their surface hydrophobicity in the blood, but the difference in the type of serum proteins associated with them.

Transport of nanoparticles across the rat nasal mucosa.

The transport of 125I-radiolabelled latex nanoparticles across the nasal mucosa of rats was studied using a range of particle sizes and surface coatings. Translocation of the particles into the blood stream was examined by means of monitoring the radiolabel associated with the particles. Particles were detected in the blood after 5 minutes. The number of particles in the blood peaked at 60 minutes, and then remained constant for a further 2 hours. The smallest particles (20 nm) showed greater uptake than the largest particles investigated (1000 nm). The total maximum uptake seen for the smallest particles was in the order of 3.25% of administered dose. 100 nm particles coated with chitosan showed an increase in both the extent and rate of uptake, with the concentration in the blood peaking at 15 minutes rather than at 60 minutes. It is suggested that transport of the particles across the nasal membrane is due mainly to a transcellular transport mechanisms by the nasal associated lymphoid tissue (NALT), especially the M-cell like cells. However, some paracellular transport cannot totally be ruled out for the smallest particles, especially if coated with chitosan.

Biliary excretion of polystyrene microspheres depends on the type of receptor-mediated uptake in rat liver.

Hepatic uptake and biliary excretion of fluorescein isothiocyanate-labeled polystyrene microspheres with a particle size of 50 nm (MS-50) were studied in rats. Liver perfusion studies revealed that not only apo-E-mediated but also asialoglycoprotein receptor-mediated uptake is involved in the mechanism of the serum protein-dependent uptake of MS-50 in the liver. The uptake of MS-50 mediated by apo-E contributes more to the total uptake of MS-50 by the hepatocytes than that via asialoglycoprotein receptor in the presence of serum in the perfusate. Furthermore, it was found that MS-50 is substantially excreted into the bile by transcytosis. The extent of exocytosis of MS-50 taken up by the hepatocytes was much higher after MS-50 was endocytosed via asialoglycoprotein receptor than after taken up via the process mediated by apo-E. On the basis of these results, a possible regulation of the intracellular sorting of ligands, depending on the receptor-mediated uptake mechanism, was inferred.

Pharmacokinetics and pharmacological effect of recombinant human granulocyte colony-stimulating factor conjugated to poly(styrene-co-maleic acid) in rats.

A new derivative of recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been synthesized by conjugating rhG-CSF to poly(styrene-co-maleic acid) (poly(styrene-co-maleic acid)-rhG-CSF) to try to avoid glomerular filtration and thus potentiate the neutrophil-proliferating activity of rhG-CSF. Poly(styrene-co-maleic acid)-rhG-CSF was highly bound to bovine serum albumin (BSA) and the molecular weight of the poly(styrene-co-maleic acid)-rhG-CSF-BSA complex was estimated to be about 90000 by gel filtration. Intravenous administration of poly(styrene-co-maleic acid)-rhG-CSF to normal rats resulted in a dose-dependent increase in neutrophil count. The neutrophil-proliferating activity of poly(styrene-co-maleic acid)-rhG-CSF was about 10 times greater than that of rhG-CSF. After intravenous injection at a dose of 5 microg protein kg(-1) the total clearance of rhG-CSF fell from 71.0 to 32.1 mLh(-1) kg(-1) following poly(styrene-co-maleic acid) modification. An isolated perfusion study in rat kidney showed that the filtered fraction of rhG-CSF was reduced by conjugation with poly(styrene-co-maleic acid). These results suggest that poly(styrene-co-maleic acid)-conjugation can potentiate the neutrophil-proliferating activity of rhG-CSF by reducing, at least in part, its renal clearance.

Mechanisms of hepatic disposition of polystyrene microspheres in rats: effects of serum depend on the sizes of microspheres.

To study the mechanisms of the hepatic disposition of polystyrene microspheres (MS), effects of serum on their hepatic disposition characteristics were investigated for MSs with particle sizes of 50 nm (MS-50) and 500 nm (MS-500) by isolated liver perfusion experiments. It was revealed that serum in the perfusate inhibited and promoted the hepatic disposition of MS-50 and MS-500 at 37 degrees C, respectively. However, pre-heating at 56 degrees C or pre-treatment with anti-C3 antibody of serum reduced the promotive effect of serum on the hepatic uptake of MS-500, suggesting that the complement system should be involved as opsonins for the hepatic uptake of MS-500. Hepatic disposition of both MSs at 4 degrees C was reduced by the addition of serum into the perfusate, which could be ascribed to the reduction of the surface hydrophobicity of MSs due to the adsorption of serum proteins onto the surface of MSs and to resultant decrease in non-specific disposition to the liver. From these results, serum was found to function both as the opsonin to enhance the hepatic uptake of MSs and as the inhibitor by reducing non-specific interaction between MSs and the plasma membrane. Whether serum promotes or inhibits the hepatic disposition of MSs would be dependent on the particle sizes of MSs.

Hepatic uptake of polystyrene microspheres in rats: effect of particle size on intrahepatic distribution.

The in vivo disposition of polystyrene microsphere (MS) with the particle size of 50 nm (MS-50) or 500 nm (MS-500) was characterized after intravenous administration to rats. A rapid elimination from systemic circulation was observed for both MSs. Tissue distribution of MS-50 and MS-500 at 1 h after intravenous injection indicated that both MSs were exclusively distributed to liver and that small but significant amounts of MS-50 and MS-500 were also distributed to lung and spleen, respectively. To investigate the intrahepatic distribution of MS, liver was separated into liver parenchymal cells (PC) and non-parenchymal cells (NPC) at 1 or 6 h after intravenous administration. The contribution of each cell fraction was dependent on both the size of MS and the time after administration. Furthermore, by separating the NPC into endothelial cells and Kupffer cells using a centrifugal elutriation method, their contribution was also evaluated. For both MSs, Kupffer cells were recognized to be mostly responsible for the hepatic uptake, although a significant amount of MS-50 (about 28% of total uptake) was taken up by PC. On the other hand, there was little contribution of PC (about 5%) to the hepatic uptake of MS-500. The endothelial cells were contributed larger to the uptake of MS-500 (about 24%) than that of MS-50 (13%).

In vitro and ex vivo platelet interactions with hydrophilic-hydrophobic poly(ethylene oxide)-polystyrene multiblock copolymers.

Hydrophilic-hydrophobic multiblock copolymers synthesized from telechelic oligomers of poly(ethylene oxide) (PEO) and polystyrene (PS) have been used to study the influence of hydrophilic and hydrophobic balance on interfacial interactions of these surfaces with blood components. In vitro coagulation assays show no inherent ability of these amphiphilic surfaces to affect contact activation or coagulation factors. In vitro platelet adhesion and release reactions from rabbit platelet-rich plasma were shown to be greatest on Biomer and PS homopolymer surfaces and least on cross-linked PEO surfaces, with the PEO-PS block copolymers demonstrating intermediate responses. These same substrates were tested in a new low-flow, low-shear arterio-artery shunt system in rabbits. Whole blood occlusion times were not a direct function of hydrophilic content as both PEO and PS homopolymers and Biomer showed short occlusion times, while PEO-PS block copolymers prolonged occlusion times considerably, depending on composition. Overall, results suggest that PEO-PS block copolymers promote unique whole blood responses in contrast to homopolymer and Biomer controls which are more complex than direct correlations to bulk hydrophilic and hydrophobic contents.