Potenziale und Grenzen der Sekundärrohstoffgewinnung – Ergebnisse der r4-Begleitforschung

The socio-economic and ecological impacts of selected projects of the BMBF funding program “r⁴ – Innovative Technologies for Resource Efficiency – Research for the Provision of Raw Materials of Strategic Economic Importance” are presented. Many, but not all, research projects indicate a potential improvement of the supply situation in Germany. In some cases, the provision of secondary raw materials is unprofitable or ecologically detrimental. These cases require a balancing between security of supply and other economic and ecological objectives.     

SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation,optimization and efficacy evaluation

One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol^®F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4?h.     

Degradable Bottlebrush Polypeptides and the Impact of their Architecture on Cell Uptake,Pharmacokinetics, and Biodistribution In Vivo

Bottlebrush polymers are highly promising as unimolecular nanomedicines due to their unique control over the critical parameters of size, shape and chemical function. However, since they are prepared from biopersistent carbon backbones, most known bottlebrush polymers are non-degradable and thus unsuitable for systemic therapeutic administration. Herein, we report the design and synthesis of novel poly(organo)phosphazene-g-poly(α-glutamate) (PPz-g-PGA) bottlebrush polymers with exceptional control over their structure and molecular dimensions (Dh ≈ 15–50 nm). These single macromolecules show outstanding aqueous solubility, ultra-high multivalency and biodegradability, making them ideal as nanomedicines. While well-established in polymer therapeutics, it has hitherto not been possible to prepare defined single macromolecules of PGA in these nanosized dimensions. A direct correlation was observed between the macromolecular dimensions of the bottlebrush polymers and their intracellular uptake in CT26 colon cancer cells. Furthermore, the bottlebrush macromolecular structure visibly enhanced the pharmacokinetics by reducing renal clearance and extending plasma half-lives. Real-time analysis of the biodistribution dynamics showed architecture-driven organ distribution and enhanced tumor accumulation. This work, therefore, introduces a robust, controlled synthesis route to bottlebrush polypeptides, overcoming limitations of current polymer-based nanomedicines and, in doing so, offers valuable insights into the influence of architecture on the in vivo performance of nanomedicines.     

Antioxidant Potential,Lipid Peroxidation Inhibition and Antimicrobial Activities of Satureja montana L. subsp. kitaibelii Extracts

The antioxidant activity of different Satureja montana L. subsp. kitaibelii extracts was tested by measuring their ability to scavenge reactive hydroxyl radical during the Fenton reaction, using ESR spectroscopy. Also, the influence of these extracts on lipid peroxyl radicals obtained during lipid peroxidation of: (I) sunflower oil (37 ºC, 3h) induced by 4,4′-azobis(4-cyanovaleric acid) (ACVA) and (II) liposomes induced by 2,2′-azobis(2- amidino-propane)dihydrochloride (AAPH) was studied. n-Butanol extract had the best antioxidant activity (100% at 0.5 mg/mL in Fenton reaction system; 89.21% at 5 mg/mL in system I; 83.38% at 5 mg/mL in system II). The antioxidant activities of the extracts significantly correlated with total phenolic content. The antimicrobial activity of Satureja montana L. subsp. kitaibelii extracts was investigated. Petroleum ether, chloroform and ethyl acetate extracts expressed a wide range of inhibiting activity against both grampositive and gram-negative bacteria.     

Synthetic Indolactam V Analogues as Inhibitors of PAR2‐Induced Calcium Mobilization in Triple‐Negative Breast Cancer Cells

Human proteinase‐activated receptor 2 (PAR2), a transmembrane G‐protein‐coupled receptor (GPCR), is an attractive target for a novel anticancer therapy, as it plays a critical role in cell migration and invasion. Selective PAR2 inhibitors therefore have potential as anti‐metastatic drugs. Knowing that the natural product teleocidin A2 is able to inhibit PAR2 in tumor cells, the goal of the present study was to elaborate structure–activity relationships and to identify potent PAR2 inhibitors with lower activity against the adverse target, protein kinase C (PKC). For this purpose, an efficient gram‐scale total synthesis of indolactam V (i.e., the parent structure of all teleocidins) was developed, and a library of derivatives was prepared. Some compounds were indeed found to exhibit high potency as PAR2 inhibitors at low nanomolar concentrations with improved selectivity (relative to teleocidin A2). The pseudopeptidic fragment bridging the C3 and C4 positions of the indole core proved to be essential for target binding, whereas activity and target selectivity depends on the substituents at N1 or C7. This study revealed novel derivatives that show high efficacy in PAR2 antagonism combined with increased selectivity.     

Immobilization of α‐amylase in polyelectrolyte complexes

Herein, we report the formation of α‐amylase containing polyelectrolyte complexes (PECs). The method for the encapsulation of α‐amylase is based on interactions between two oppositely charged polyelectrolytes, poly(acrylic acid) (PAA) and polyethylenimine (PEI). We could show that electrostatic interactions ensure the incorporation of the enzyme into the formed polyelectrolyte complexes. The encapsulation has no negative effect on enzyme activity and protects against denaturation of the enzyme initiated by low pH values. The resulting PECs are 150–250 nm in size with narrow size distribution, appear in a spherical shape and are colloidally stable. The complexation of both polyelectrolytes and the immobilization of α‐amylase are investigated using fractionating techniques mainly the analytical ultracentrifugation and asymmetrical‐flow field‐flow fractionation. The formation of PECs represents a simple method for the encapsulation of α‐amylase without the use of organic solvents and requires no additional purifications steps. This one‐step approach, yielding high encapsulation efficiencies, shows the potential as a drug delivery system for sensitive hydrophilic actives in future. α‐amylase is immobilized in polyelectrolyte complexes made of polyethylenimine and poly(acrylic acid). Optimized encapsulation conditions and the resulting polyelectrolyte complexes are investigated via determination of IEP, α‐amylase activity assays, nanoDSC measurements, zeta potential values, dynamic light scattering, microscopy, and fractionating techniques. The encapsulated enzyme is protected against denaturation initiated by low pH values. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45036.     

The health effects of improvements to housing: A longitudinal study

Although housing conditions were an integral part of the emergence of the Public Health movement, there has been relatively little research on the relationship between housing and health compared to that on social inequalities in general. This is surprising in view of the fact that one of the major links between social inequalities and health is adverse housing conditions. Findings from previous investigations in several countries of the presence of damp and mould in housing and symptoms in the occupants have indicated that the associations may well be causal. However, there have been no studies which have assessed the health of the residents before and after the elimination of dampness/mould. This paper describes a longitudinal study designed to evaluate the effects of an improved heating system on the symptoms of children living on a peripheral housing estate. The results suggested that the elimination of dampness/mould prevented a further deterioration in health rather than bringing about an improvement. The presence of other factors known to influence health status, such as financial difficulties and other housing problems, may have offset any benefits arising from the new heating system. The methodological issues that arose in conducting the study in an area of severe social disadvantage are described. It is suggested that the complexity of the interactions between bad housing and low income, should not detract attention from the need for intersectoral co‐operation to address the issue.     

Total mercury,methylmercury and selenium in mercury polluted areas in the province Guizhou,China

The province of Guizhou in Southwestern China is currently one of the world's most important mercury production areas. Emissions of mercury from the province to the global atmosphere have been estimated to be approximately 12% of the world total anthropogenic emissions. The main objective of this study was to assess the level of contamination with Hg in two geographical areas of Guizhou province. Mercury pollution in the areas concerned originates from mercury mining and ore processing in the area of Wanshan, while in the area of Quingzhen mercury pollution originates from the chemical industry discharging Hg through wastewaters and emissions to the atmosphere due to coal burning for electricity production. The results of this study confirmed high contamination with Hg in soil, sediments and rice in the Hg mining area in Wanshan. High levels of Hg in soil and rice were also found in the vicinity of the chemical plant in Quingzhen. The concentrations of Hg decreased with distance from the main sources of pollution considerably. The general conclusion is that Hg contamination in Wanshan is geographically more widespread, due to deposition and scavenging of Hg from contaminated air and deposition on land. In Quingzhen Hg contamination of soil is very high close to the chemical plant but the levels reach background concentrations at a distance of several km. Even though the major source of Hg in both areas is inorganic Hg, it was observed that active transformation of inorganic Hg to organic Hg species (MeHg) takes place in water, sediments and soils. The concentration of Hg in rice grains can reach up to 569 microg/kg of total Hg of which 145 microg/kg was in MeHg form. The percentage of Hg as MeHg varied from 5 to 83%. The concentrations of selenium can reach up to 16 mg/kg in soil and up to 1 mg/g in rice. A correlation exists between the concentration of Se in soil and rice, indicating that a portion of Se is bioavailable to plants. No correlation between Hg and Se in rice was found. Exposure of the local population to Hg may occur due to inhalation of Hg present in air (in particular in Hg mining area) and consumption of Hg contaminated food (in particular rice and fish) and water. Comparison of intake through these different routes showed that the values of Hg considerably exceed the USA EPA Reference Concentration (RfC) for chronic Hg exposure (RfC is 0.0004 mg/m(3)) close to the emission sources. Intake of Hg through food consumption, particularly rice and fish, is also an important route of Hg exposure in study area. In general, it can be concluded that the population mostly at risk is located in the vicinity of smelting facilities, mining activities and close to the waste disposal sites in the wider area of Wanshan. In order to assess the real level of contamination in the local population, it is recommended that biomonitoring should be performed, including Hg and MeHg measurements in hair, blood and urine samples.