Simultaneous LC−UV Analysis of Mirodenafil and Its Two Main Metabolites in Rat Plasma and Urine, and in Tissue Homogenates

A simple, rapid, and reproducible isocratic reversed-phase LC method has been established for simultaneous analysis of mirodenafil and its two main metabolites, SK3541 and SK3544, in rat plasma, urine, and tissue homogenates. Samples were deproteinized with acetonitrile containing sildenafil (internal standard). The compounds were separated on a C₁₈ column with 52:48 (v/v) 0.02 m ammonium acetate buffer (pH 6)—acetonitrile as mobile phase at a flow rate of 1.4 mL min^?1. UV detection was at 254 nm and detection limits of mirodenafil, SK3541, and SK3544 in plasma were 0.03, 0.05, and 0.1 μg mL^?1, respectively. The method is applicable to pharmacokinetic studies of mirodenafil and its metabolites in rats.     

Synthesis and Microcontact Printing of Dual End‐Functionalized Mucin‐like Glycopolymers for Microarray Applications

Click to view : Glycopolymers can be used to display glycans on microarrays in native‐like architectures. The structurally uniform alkyne‐terminated mucin mimetic glycopolymers (see picture; TR=fluorophore) were printed on azide‐functionalized chips by microcontact printing in the presence of a copper catalyst. The surface‐bound glycopolymers bind lectins in a ligand‐specific manner.

     

Poly[lactic‐co‐(glycolic acid)]‐Grafted Hyaluronic Acid Copolymer Micelle Nanoparticles for Target‐Specific Delivery of Doxorubicin

PLGA‐grafted HA copolymers were synthesized and utilized as target specific micelle carriers for DOX. For grafting hydrophobic PLGA chains onto the backbone of hydrophilic HA, HA was solubilized in an anhydrous DMSO by nano‐complexing with dimethoxy‐PEG. The carboxylic groups of HA were chemically grafted with PLGA, producing HA‐g‐PLGA copolymers. Resultant HA‐g‐PLGA self‐assembled in aqueous solution to form multi‐cored micellar aggregates and DOX was encapsulated during the self‐assembly. DOX‐loaded HA‐g‐PLGA micelle nanoparticles exhibited higher cellular uptake and greater cytotoxicity than free DOX for HCT‐116 cells that over‐expressed HA receptor, suggesting that they were taken up by the cells via HA receptor‐mediated endocytosis.

     

Functional Polymers for Targeted Delivery of Nucleic Acid Drugs

Cationic polymers have been chemically modified with a variety of targeting molecules such as peptides, proteins, antibodies, sugars and vitamins for targeted delivery of nucleic acid drugs to specific cells. Stimuli‐sensitive polymers exhibiting different size, charge and conformation in response to physiological signals from specific cells have also been utilized for targeted delivery. To achieve target‐specific delivery of nucleic acids, conjugation chemistry is critical to produce stable nanosized polyplexes tethered with cell‐recognizable ligands for facile cellular uptake via a receptor‐mediated endocytic pathway. In this review, synthetic strategies of functional cationic polymers with various targeting ligands are presented.

     

Influences of poly(lactic acid)‐grafted carbon nanotube on thermal,mechanical, and electrical properties of poly(lactic acid)

Poly(lactic acid)‐grafted multiwalled carbon nanotubes (MWNT‐g‐PLA) were prepared by the direct melt‐polycondensation of L ‐lactic acid with carboxylic acid‐functionalized MWNT (MWNT‐COOH) and then mixed with a commercially available neat PLA to prepare PLA/MWNT‐g‐PLA nanocomposites. Morphological, thermal, mechanical, and electrical characteristics of PLA/MWNT‐g‐PLA nanocomposites were investigated as a function of the MWNT content and compared with those of the neat PLA, PLA/MWNT, and PLA/MWNT‐COOH nanocomposites. It was identified from FE‐SEM images that PLA/MWNT‐g‐PLA nanocomposites exhibit good dispersion of MWNT‐g‐PLA in the PLA matrix, while PLA/MWNT and PLA/MWNT‐COOH nanocomposites display MWNT aggregates. As a result, initial moduli and tensile strengths of PLA/MWNT‐g‐PLA composites are much higher than those of neat PLA, PLA/MWNT, and PLA/MWNT‐COOH, which stems from the efficient reinforcing effect of MWNT‐g‐PLA in the PLA matrix. In addition, the crystallization rate of PLA/MWNT‐g‐PLA nanocomposites is faster than those of neat PLA, PLA/MWNT, and PLA/MWNT‐COOH, since MWNT‐g‐PLA dispersed in the PLA matrix serves efficiently as a nucleating agent. It is interesting that, unlike PLA/MWNT nanocomposites, surface resistivities of PLA/MWNT‐g‐PLA nanocomposites did not change noticeably depending on the MWNT content, demonstrating that MWNTs in PLA/MWNT‐g‐PLA are wrapped with the PLA chains of MWNT‐g‐PLA. Copyright © 2008 John Wiley & Sons, Ltd.     

Engineering enzyme specificity using computational design of a defined-sequence library

Engineered biosynthetic pathways have the potential to produce high-value molecules from inexpensive feedstocks, but a key limitation is engineering enzymes with high activity and specificity for new reactions. Here, we developed a method for combining structure-based computational protein design with library-based enzyme screening, in which inter-residue correlations favored by the design are encoded into a defined-sequence library. We validated this approach by engineering a glucose 6-oxidase enzyme for use in a proposed pathway to convert D-glucose into D-glucaric acid. The most active variant, identified after only one round of diversification and screening of only 10,000 wells, is approximately 400-fold more active on glucose than is the wild-type enzyme. We anticipate that this strategy will be broadly applicable to the discovery of new enzymes for engineered biological pathways.     

Passive regulation of volume‐flow ratio for microfluidic streams with different hydrophilicity and viscosity

Biochemical solutions have a wide range of hydrophilicity (contact angle and surface tension) and viscosity. A critical challenge is that microfluidic systems typically need expensive or complex pumps to control the various parallel biochemical streams. In this study, without using any pumps, we present a simple scheme that controls the ratio of the volumetric flow rate (VFR) of the parallel streams that have highly different hydrophilicity and viscosity. We accomplish this process by using capillarity to drive and merge two streams, and by regulating relative flow resistance to control the VFR ratio. Our results will significantly simplify the control of the VFR ratio for the various biochemical solutions that are used in microfluidic applications.     

SSA-MOA: a novel CTC isolation platform using selective size amplification (SSA) and a multi-obstacle architecture (MOA) filter

Circulating tumor cells (CTCs) have gained increasing attention as physicians and scientists learn more about the role these extraordinarily rare cells play in metastatic cancer. In developing CTC technology, the critical criteria are high recovery rates and high purity. Current isolation methods suffer from an inherent trade-off between these two goals. Moreover, ensuring minimal cell stress and robust reproducibility is also important for the clinical application of CTCs. In this paper, we introduce a novel CTC isolation technology using selective size amplification (SSA) for target cells and a multi-obstacle architecture (MOA) filter to overcome this trade-off, improving both recovery rate and purity. We also demonstrate SSA-MOA's advantages in minimizing cell deformation during filter transit, resulting in more stable and robust CTC isolation. In this technique, polymer microbeads conjugated with anti-epithelial cell adhesion molecules (anti-EpCAM) were used to selectively size-amplify MCF-7 breast cancer cells, definitively differentiating from the white blood cells (WBCs) by avoiding the size overlap that compromises other size selection methods. 3 μm was determined to be the optimal microbead diameter, not only for size discrimination but also in maximizing CTC surface coverage. A multi-obstacle architecture filter was fabricated using silicon-on-glass (SOG) technology-a first such application of this fabrication technique-to create a precise microfilter structure with a high aspect ratio. The filter was designed to minimize cell deformation as simulation results predicted that cells captured via this MOA filter would experience 22% less moving force than with a single-obstacle architecture. This was verified by experiments, as we observed reliable cell capture and reduced cell deformation, with a 92% average recovery rate and 351 peripheral blood leukocytes (PBL) per millilitre (average). We expect the SSA-MOA platform to optimize CTC recovery rates, purity, and stability, increasing the sensitivity and reliability of such tests, thereby potentially expanding the utilization of CTC technologies in the clinic.     

J-aggregation induced low bandgap anthracene-based conjugated molecule for solution-processed solar cells

A new anthracene-based X-shaped conjugated molecule, HBTATHT, was synthesized. Thin film transistors based on unannealed HBTATHT showed a carrier mobility of 0.15 cm(2) V(-1) s(-1) (I(on/off) = 7.9 × 10(6)). Further, a solution processed solar cell made of HBTATHT exhibited promising power conversion efficiencies of 4.84% and 4.70% with PC(61)BM (1?:?0.8 wt ratio) and PC(71)BM (1?:?0.6 wt ratio), respectively.