Physicochemical properties and bio-interfacial interactions of surface modified PDLLA-PAMAM linear dendritic block copolymers

Here, we demonstrate the applicability of self-assembling linear-dendritic block copolymers (LDBCs) and their nanoaggregates possessing varied surfaces as therapeutic nanocarriers. These LDBCs are comprised of a hydrophobic, linear polyester chemically coupled to a hydrophilic dendron polyamidoamine (PAMAM)—the latter of which acts as the surface of the self-assembled nanoaggregate in aqueous media. To better understand how surface charge density affects the overall operability of these nanomaterials, we modified the nanoaggregate surface to yield cationic (NH₃⁺), neutral (OH), and anionic (COO⁻) surfaces. The effect of these modifications on the physicochemical properties (i.e., size, morphology, and surface charge density), colloidal stability, and cellular uptake mechanism of the polymeric nanocarrier were investigated. This comparative study demonstrates the viability of nanoaggregates formed from PDLLA-PAMAM LDBCs to serve as nanocarriers for applications in drug delivery.     

NMR Spin Trapping: Insight into the Hidden Life of Free Radical Adducts

In our original work (V. Khramtsov, L.J. Berliner and T.L. Clanton, Magn. Reson. Med. 42:228??34, 1999), a ³¹P nuclear magnetic resonance spin trapping (ST NMR) approach aimed to overcome comparatively short lifetimes of the paramagnetic adducts by detecting stable diamagnetic adducts of the degradation of phosphorous-containing nitrone was proposed. High stability of the NMR adducts of the nitrone spin traps with C-centered radicals and the ability to track their origin from paramagnetic adducts make ST NMR a valuable tool for the studies of these radicals in chemical and biological systems. Complementary ST NMR and electron paramagnetic resonance studies of the nitrone adducts derived from the addition of O- and S-centered radicals and nucleophiles revealed new insights into the pathways of the paramagnetic and diamagnetic adduct formation and degradation. In particular, use of ST NMR allowed for observation of reversible nucleophilic addition to the nitrones. On one hand, nucleophilic addition may result in a possible spin trapping artifact via the Forrester–Hepburn mechanism; whereas, on the other hand, the reverse reaction provides the key step in the “recycling??mechanism that is important for the antioxidant actions of the nitrones.     

Soft-lithographic approach to functionalization and nanopatterning oxide-free silicon

We report a simple, reliable high-throughput method for patterning passivated silicon with reactive organic monolayers and demonstrate selective functionalization of the patterned substrates with both small molecules and proteins. The approach completely protects silicon from chemical oxidation, provides precise control over the shape and size of the patterned features in the 100 nm domain, and gives rapid, ready access to chemically discriminated patterns that can be further functionalized with both organic and biological molecules.     

Spectra of Cayley graphs of complex reflection groups

Renteln proved that the eigenvalues of the distance matrix of a Cayley graph of a real reflection group with respect to the set of all reflections are integral and provided a combinatorial formula for some such spectra. We prove the eigenvalues of the distance, adjacency, and codimension matrices of Cayley graphs of complex reflection groups with connection sets consisting of all reflections are integral and provide a combinatorial formula for the codimension spectra for a family of monomial complex reflection groups.     

Biocatalytic microcontact printing

Immobilized biocatalytic lithography is presented as an application of soft lithography. In traditional microcontact printing, diffusion limits resolution of pattern transfer. By using an immobilized catalyst, the lateral resolution of microcontact printing would depend only on the length and flexibility of the tether (<2 nm) as opposed to diffusion (>100 nm). In the work, exonuclease reversibly immobilized on a relief-patterned stamp is used to ablate ssDNA monolayers Percent of ablation was determined via confocal fluorescence microscopy to be approximately 70%.     

Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor,EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development

There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed for other species. Considering the diversity of species and breeds in companion animal medicine, comprehensive PK exposures in the companion animal patient is often lacking. The purpose of this paper was to assess the pharmacokinetics after oral and intravenous dosing in domesticated animal species (dogs, cats, and horses) of a novel soluble epoxide hydrolase inhibitor, EC1728, being developed for the treatment of pain in animals. Results: Intravenous and oral administration revealed that bioavailability was similar for dogs, and horses (42 and 50% F) but lower in mice and cats (34 and 8%, respectively). Additionally, clearance was similar between cats and mice, but >2× faster in cats vs. dogs and horses. Efficacy with EC1728 has been demonstrated in mice, dogs, and horses, and despite the rapid clearance of EC1728 in cats, analgesic efficacy was demonstrated in an acute pain model after intravenous but not oral dosing. Conclusion: These results demonstrate that exposures across species can vary, and investigation of therapeutic exposures in target species is needed to provide adequate care that addresses efficacy and avoids toxicity.     

Gated magnetic resonance imaging of acute myocardial ischemia in dogs: application of multiecho techniques and contrast enhancement with GD DTPA

ECG gated magnetic resonance images were obtained in six canines prior to and immediately following occlusion of either the LAD or circumflex coronary artery using a surgically placed snare. Multiecho and single-echo acquisition techniques were utilized 0.25 mmol/kg Gd DTPA was injected as an IV bolus 1 hr following coronary artery ligation. In two animals, the region of ischemic myocardium was clearly visualized on multiecho technique without the use of intravenous contrast. The ischemic zone could be best identified on images with a long TE of 120 msec. Contrast enhancement with Gd DTPA enabled visualization of the ischemic myocardium in all six canines. Administration of Gd DTPA, a perfusion agent, improved both detectability and definition of the myocardial lesions.     

Lower Activation Energy for Catalytic Reactions through Host–Guest Cooperation within Metal–Organic Frameworks

Industrial synthesis is driven by a delicate balance of the value of the product against the cost of production. Catalysts are often employed to ensure product turnover is economically favorable by ensuring energy use is minimized. One method, which is gaining attention, involves cooperative catalytic systems. By inserting a flexible polymer into a metal–organic framework (MOF) host, the advantages of both components work synergistically to create a composite that efficiently fixes carbon dioxide to transform various epoxides into cyclic carbonates. The resulting material retains high yields under mild conditions with full reusability. By quantitatively studying the kinetic rates, the activation energy was calculated, for a physical mixture of the catalyst components to be about 50 % higher than that of the composite. Through the unification of two catalytically active components, a new opportunity opens up for the development of synergistic systems in multiple applications.     

Selective Array-Based Sensing of Anabolic Steroids in Aqueous Solution by Host–Guest Reporter Complexes

Arrayed complexes of a water-soluble deep cavitand and two fluorescent indicators show selective sensing of anabolic-androgenic steroids in aqueous environments. By combining the host–guest complexes with small amounts of heavy metal ions, discrimination between steroids that vary in structure by only a single π bond is possible. The sensing occurs through a triggered aggregation mechanism, which can be mediated by both the presence of metal ions and the steroids. The use of both “turn-on” and “turn-off” fluorophores is essential for good discrimination. As low as 10 μm steroid can be detected, and the discrimination is selective in steroid samples spiked into human urine.