High Loading Efficiency and Controlled Release of Bioactive Immunotherapeutic Proteins Using Vaterite Nanoparticles

Nanoparticles may limit off-tumor/on-target ubiquitous activation of signaling by protein-based drugs. However, many challenges still exist in the design of a nanoparticle for protein delivery. In this study, conditions to establish vaterite nanoparticles as a pH-sensitive drug delivery system (DDS) for encapsulated protein drugs are comprehensively evaluated. Low coprecipitation pH of vaterite and protein prevents protein denaturation and yields high loading efficiency. Unprotected vaterite recrystallizes in aqueous solutions within 3 h to calcite and releases the loaded protein completely, but surface-modified particles with carboxyl groups containing polymers prove stable for more than 5 months. Notably, modification of vaterite with sulfonated polymers increases the loading of cationic proteins by a multiple. A system is developed for vaterite exposure to (pH) conditions under body-like-flow rates, with the dissolution of vaterite and simultaneous release of active proteins at tumor microenvironmental pH reaching up to 80% and only 20% at physiological pH within 2 h. Importantly, the immunomodulatory protein tumor necrosis factor preserves its native structure and fully retains functional activity in vitro after release from the particles. In conclusion, the studies described here provide a framework for the development of vaterite-based DDS as a carrier for bioactive protein-based therapeutics.     

ChemInform Abstract: A Matrix Isolation and Computational Study of Molecular Palladium Fluorides: Does PdF6 Exist?

Binary palladium fluorides from PdF to PdF₆ are investigated by matrix‐isolation methods using thermal evaporation and laser ablation to generate Pd atoms for reaction with F₂‐doped Ar and Ne matrices as well as neat F₂ matrices.     

ChemInform Abstract: Investigation of Praseodymium Fluorides: A Combined Matrix‐Isolation and Quantum‐Chemical Study.

Reaction products of laser‐ablated praseodymium atoms with fluorine in excess neon, argon, krypton, or neat fluorine at 4—10 K are investigated by IR spectroscopy and quantum chemical DFT and coupled‐cluster calculations.     

Creep deformation at crack tips in elastic-viscoplastic solids

The evaluation of crack growth tests under creep conditions must be based on the stress analysis of a cracked body taking into account elastic, plastic and creep deformation. In addition to the well-known analysis of a cracked body creeping in secondary (steady-state) creep, the stress field at the tip of a stationary crack is calculated for primary (strain-hardening) or tertiary (strain-softening) creep of the whole specimen. For the special hardening creep-law considered, a path-independent integral C¹_h, can be defined which correlates the near-tip field to the applied load.It is also shown how, after sudden load application, creep strains develop in the initially elastic or, for a higher load level, plastic body. Characteristic times are derived to distinguish between short times when the creep-zones, in which creep strains are concentrated, are still small, and long times when the whole specimen creeps extensively in primary and finally in secondary and tertiary creep. Comparing the creep-zone sizes with the specimen dimensions or comparing the characteristic times with the test duration, one can decide which deformation mechanism prevails in the bulk of the specimen and which load parameter enters into the near-tip stress field and determines crack growth behavior. The governing load parameter is the stress intensity factor K₁ if the bulk of the specimen is predominantly elastic and it is the J-integral in a fully-plastic situation when large creep strains are still confined to a small zone. The C¹_h-integral applies if the bulk of the specimen deforms in primary or tertiary creep, and C¹ is the relevant load parameter for predominantly secondary creep of the whole specimen.     

Selective heterolytic P-P bond cleavage of white phosphorus by a frustrated carbene-borane Lewis pair

Frustrated carbene-borane Lewis pairs are able to affect the selective cleavage of one of the six P-P bonds in white phosphorus (P(4)) to afford an adduct, in which an abnormal carbene of the imidazolium-4-yl type and B(C(6)F(5))(3) are bound in a trans,trans fashion to a butterfly-like bicyclo[1.1.0]tetraphosphabutane moiety.     

Simultaneous analysis of 70 pesticides using HPlc/MS/MS: a comparison of the multiresidue method of Klein and Alder and the QuEChERS method

Since 2003, two new multipesticide residue methods for screening crops for a large number of pesticides, developed by Klein and Alder and Anastassiades et al. (Quick, Easy, Cheap, Effective, Rugged, and Safe; QuEChERS), have been published. Our intention was to compare these two important methods on the basis of their extraction efficiency, reproducibility, ruggedness, ease of use, and speed. In total, 70 pesticides belonging to numerous different substance classes were analyzed at two concentration levels by applying both methods, using five different representative matrixes. In the case of the QuEChERS method, the results of the three sample preparation steps (crude extract, extract after SPE, and extract after SPE and acidification) were compared with each other and with the results obtained with the Klein and Alder method. The extraction efficiencies of the QuEChERS method were far higher, and the sample preparation was much quicker when the last two steps were omitted. In most cases, the extraction efficiencies after the first step were approximately 100%. With extraction efficiencies of mostly less than 70%, the Klein and Alder method did not compare favorably. Some analytes caused problems during evaluation, mostly due to matrix influences.     

Accumulation of Stark-decelerated NH molecules in a magnetic trap

Here we report on the accumulation of ground-state NH molecules in a static magnetic trap. A pulsed supersonic beam of NH (a¹Δ) radicals is produced and brought to a near standstill at the center of a quadrupole magnetic trap using a Stark decelerator. There, optical pumping of the metastable NH radicals to the X³Σ^? ground state is performed by driving the spin-forbidden A³Π ← a¹Δ transition, followed by spontaneous A → X emission. The resulting population in the various rotational levels of the ground state is monitored via laser induced fluorescence detection. A substantial fraction of the ground-state NH molecules stays confined in the several milliKelvin deep magnetic trap. The loading scheme allows one to increase the phase-space density of trapped molecules by accumulating packets from consecutive deceleration cycles in the trap. In the present experiment, accumulation of six packets is demonstrated to result in an overall increase of only slightly over a factor of two, limited by the trap-loss and reloading rates.     

Determination of potentially toxic heavy metals in traditionally used medicinal plants for HIV/AIDS opportunistic infections in Ngamiland District in Northern Botswana

The determination of four potentially toxic heavy metals, arsenic, chromium, lead and nickel in twelve plant species used for the treatment of perceived HIV and AIDS-associated opportunistic infections by traditional healers in Ngamiland District in Northern Botswana, a metal mining area, was carried out using atomic absorption spectrometry. The medicinal plants; Dichrostachys cinerea, Maerua angolensis, Mimusops zeyheri, Albizia anthelmintica, Plumbago zeylanica, Combretum imberbe, Indigofera flavicans, Clerodendrum ternatum, Solanum panduriforme, Capparis tomentosa, Terminalia sericea and Maytenus senegalensis contained heavy metals in varying quantities: arsenic 0.19–0.54 μg g⁻¹, chromium 0.15–1.27 μg g⁻¹, lead 0.12–0.23 μg g⁻¹ and nickel 0.09–0.21 μg g⁻¹ of dry weight. Chromium was found to be the most abundant followed by arsenic and lead. Nickel was undetectable in nine plant species. M. senegalensis contained the largest amounts of arsenic, chromium and lead. All metals determined were below the WHO permissive maximum levels. The possible maximum weekly intakes of the heavy metals following treatment regimes were insignificant compared to the provisional tolerable weekly intake levels recommended by WHO and the Joint FAO/WHO Expert Committee on Food Additives. This suggests that heavy metal exposure to patients originating from consumption of traditional medicinal plant preparations is within non health-compromising limits.