Self-assembled nanostructures obtained from natural and synthetic amphiphiles serve as mimics of biological membranes and enable the delivery of drugs, proteins, genes, and imaging agents. Yet the precise molecular arrangements demanded by these functions are difficult to achieve. Libraries of amphiphilic Janus dendrimers, prepared by facile coupling of tailored hydrophilic and hydrophobic branched segments, have been screened by cryogenic transmission electron microscopy, revealing a rich palette of morphologies in water, including vesicles, denoted dendrimersomes, cubosomes, disks, tubular vesicles, and helical ribbons. Dendrimersomes marry the stability and mechanical strength obtainable from polymersomes with the biological function of stabilized phospholipid liposomes, plus superior uniformity of size, ease of formation, and chemical functionalization. This modular synthesis strategy provides access to systematic tuning of molecular structure and of self-assembled architecture.
The blood-brain barrier efficiently controls the entry of drug molecules into the brain. We describe a feasible means to achieve carrier-mediated drug transport into the rat brain via the specific, large neutral amino acid transporter (LAT1) by conjugating a model compound to L-tyrosine. A hydrophilic drug, ketoprofen, that is not a substrate for LAT1 was chosen as a model compound. The mechanism and the kinetics of the brain uptake of the prodrug were determined with an in situ rat brain perfusion technique. The brain uptake of the prodrug was found to be concentration-dependent. In addition, a specific LAT1 inhibitor significantly decreased the brain uptake of the prodrug. Therefore, our results reveal for the first time that a drug-substrate conjugate is able to transport drugs into the brain via LAT1.
Well-defined dendronized cellulose substrates displaying multiple representations of dual-functionality were constructed by taking advantage of the efficiency of the click reaction combined with traditional anhydride chemistry. First, activated cellulose surfaces were decorated with several generations of dendrons, and their peripheral reactive groups were subsequently reacted with a trifunctional orthogonal monomer. The generated substrate tool box was successfully explored by accurately tuning the surface function using a versatile orthogonal dual postfunctionalization approach. In general, the reactions were monitored by using a click-dye reagent or a quartz crystal microbalance (QCM) technique, and the resulting surfaces were well-characterized using XPS, FT-IR, and contact angle measurements. Utilizing this approach two different surfaces have been obtained; that is, triethylenglycol oligomers and amoxicillin molecules were efficiently introduced to the dendritic surface. As a second example, mannose-decorated hydroxyl functional surfaces illustrated their potential as biosensors by multivalent detection of lectin protein at concentration as low as 5 nM.
Sequential extraction method was applied to lignins from hardwood and softwood isolated by kraft and VTT organosolv processes. Solvent extraction was found to fractionate lignin according to the molecular weight: small molecular weight lignin is dissolved in the organic solvents and the lignin with higher molecular weight is enriched into the residue. Isolated acetone fractions of lignin are more homogeneous with narrow molecular weight distributions. Based on the 31 P NMR results, both total hydroxyl content and the content of phenolic hydroxyl units are higher in the acetone fraction than in the residue. Pyrolysis-GC/MS of all lignins showed that p-hydroxy phenols are enriched to the residues. Preferential dissolution of syringyl type lignin in acetone was observed for hardwood kraft lignin, whereas the opposite behavior was seen for the hardwood organosolv lignin. Glass transition temperatures of all acetone soluble fractions were notably low compared to starting and residue lignins, which gives possibilities for future applications as a material with specific properties.
The brain uptake of solutes is efficiently governed by the blood-brain barrier (BBB). The BBB expresses a number of carrier-mediated transport mechanisms, and new knowledge of these BBB transporters can be used in the rational targeted delivery of drug molecules for active transport. One attractive approach is to conjugate an endogenous transporter substrate to the active drug molecule to utilize the prodrug approach. In the present study, ketoprofen and indomethacin were conjugated with glucose and the brain uptake mechanism of the prodrugs was determined with the in situ rat brain perfusion technique. Two of the prodrugs were able to significantly inhibit the uptake of glucose transporter (GluT1)-mediated uptake of glucose, thereby demonstrating affinity to the transporter. Furthermore, the prodrugs were able to cross the BBB in a temperature-dependent manner, suggesting that the brain uptake of the prodrugs is carrier-mediated.
High performance electron cyclotron resonance (ECR) ion sources, such as VENUS (Versatile ECR for NUclear Science), produce large amounts of x-rays. By studying their energy spectra, conclusions can be drawn about the electron heating process and the electron confinement. In addition, the bremsstrahlung from the plasma chamber is partly absorbed by the cold mass of the superconducting magnet, adding an extra heat load to the cryostat. Germanium or NaI detectors are generally used for x-ray measurements. Due to the high x-ray flux from the source, the experimental setup to measure bremsstrahlung spectra from ECR ion sources is somewhat different from that for the traditional nuclear physics measurements these detectors are generally used for. In particular, the collimation and background shielding can be problematic. In this paper, we will discuss the experimental setup for such a measurement, the energy calibration and background reduction, the shielding of the detector, and collimation of the x-ray flux. We will present x-ray energy spectra and cryostat heating rates depending on various ion source parameters, such as confinement fields, minimum B-field, rf power, and heating frequency.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.