A Microfluidic Co-Flow Route for Human Serum Albumin-Drug–Nanoparticle Assembly

Nanoparticles are widely studied as carrier vehicles in biological systems because their size readily allows access through cellular membranes. Moreover, they have the potential to carry cargo molecules and as such, these factors make them especially attractive for intravenous drug delivery purposes. Interest in protein-based nanoparticles has recently gained attraction due to particle biocompatibility and lack of toxicity. However, the production of homogeneous protein nanoparticles with high encapsulation efficiencies, without the need for additional cross-linking or further engineering of the molecule, remains challenging. Herein, we present a microfluidic 3D co-flow device to generate human serum albumin/celastrol nanoparticles by co-flowing an aqueous protein solution with celastrol in ethanol. This microscale co-flow method resulted in the formation of nanoparticles with a homogeneous size distribution and an average size, which could be tuned from ≈100 nm to 1 μm by modulating the flow rates used. We show that the high stability of the particles stems from the covalent cross-linking of the naturally present cysteine residues within the particles formed during the assembly step. By choosing optimal flow rates during synthesis an encapsulation efficiency of 75±24 % was achieved. Finally, we show that this approach achieves significantly enhanced solubility of celastrol in the aqueous phase and, crucially, reduced cellular toxicity.     

Novel betulin derivatives inhibit IFN-γ and modulates COX-2 expression

Abstract

Betulin (BE) is a pentacyclic triterpenes, obtained from natural sources and with several biological activities described, such as anti-tumoral and anti-inflammatory activities. The BE esterification at hydroxyl group (C-3 and C-28) resulted in five new ester derivatives with different numbers of carbons or halogens (chlorine and fluorine). Among these BE derivatives, two (2a e 2c) were able to significantly decrease IFN-g (*p?=?0.0391; **p?=?0.0156) and 2c modulated the expression of COX-2 better than Dexamethasone (DEXA). Regarding to cytotoxic assay, the best results were obtained for BE without modifications, with emphasis on tumoral cell lines Raji and MCF-7. The derivatives 2a and 2c showed immunomodulation activity (for the cytokines IFN-g). The presence of chorine in BE seems to be important for the ability of modulate COX-2 expression, since the ester chloride derivative 2c at 100?μM is more powerful inhibitor of COX-2 than DEXA.     

Global analysis of the dynamics of a mathematical model to intermittent HIV treatment

The aim of this paper is to study the qualitative dynamics of a piecewise smooth system modeling the intermittent treatment of the human immunodeficiency virus. Typical singularities and closed orbits are observable, and we quantitatively explore the dynamics around those singularities and closed orbits. Moreover, we conclude that this protocol always will be successful since the trajectory passing through any initial condition converges to one of these distinguished orbits. Our formal mathematical results corroborate the real-world observation, where the virus is not eliminated, but the number of infected cells is controlled around a specific value.

     

Complexes of vanadyl and uranyl ions with the chelating groups of humic matter

The uranyl and vanadyl complexes formed with salicylic, phthalic and 3,4-dihydroxybenzoic acids have been studied by potentiometry in order to determine the stability constants of the M(m)L(n) species formed in solution, and the constants for the hydrolysis and polymeric complexes, at 25.0 degrees , in 0.10, 0.40 and 0.70M sodium perchlorate. MINIQUAD was used to process the data to find the best models for the species in solution, and calculate the formation constants. The uranyl-salicylic acid system was also studied by spectrophotometry and the program SQUAD used to process the data obtained. The best models for these systems show that co-ordination of the uranyl ion by carboxylate groups is easier than for the vanadyl ion, whereas the vanadyl ion seems to form more stable complexes with phenolate groups. Both oxo-cations seem to tend to hydrolyse rather than form complexes when the L:M ratios are greater than unity. Although the change in the constants with ionic strength is small, the activity coefficients of the salicylate and phthalate species have been calculated at ionic strengths 0.40 and 0.70M, along with the interaction parameters with Na(+), from the stability constants found for the species ML and H(2)L, according to the Br?nsted-Guggenheim expression.     

The Borsuk�CUlam theorem for homotopy spherical space forms

In this work, we show for which odd-dimensional homotopy spherical space forms the Borsuk–Ulam theorem holds. These spaces are the quotient of a homotopy odd-dimensional sphere by a free action of a finite group. Also, the types of these spaces which admit a free involution are characterized. The case of even-dimensional homotopy spherical space forms is basically known.     

Influence of surface composition on hydrogen peroxide decomposition catalyzed by Co(II) aminopyridine-supported compounds on amorphous silica gel

Cobalt compounds supported on 2-, 3-, and 4-aminopyridine-modified silica surfaces, named Sil2Co, Sil3Co, and Sil4Co, respectively, were used to catalyze the decomposition of hydrogen peroxide on ethanolic solutions at 293, 298, and 303 K. The calculated k values (x10(-4) s(-1)) for Sil2Co, Sil3Co, and Sil4Co are 0.65, 1.24, and 4.78 (293 K); 1.23, 1.87, and 6.33 (298 K); and 1.80, 2.80, and 10.30 (303 K), respectively. All obtained results evidence that such decomposition is a first-order reaction. Zinc-, nickel-, and copper-supported compounds were also tested, but exhibited a very low catalytic activity. By using the k values at 298 and 303 K, and employing the equation ln (k1/k2) = E(a)/R(1/T2-1/T1), the activation energy values for the considered reaction were Sil2Co = 57.20, Sil3Co = 60.60, and Sil4Co = 73.10 kJ mol(-1), respectively. The low values calculated for E(a) are in agreement with a free-radical mechanism.     

Square-wave voltammetric techniques for determination of psychoactive 1,4-benzodiazepine drugs

Direct square-wave voltammetry (SWV) and square-wave cathodic stripping voltammetry (SWCSV) at hanging mercury drop electrodes have been developed for determination of the psychoactive 1,4-benzodiazepine compounds clonazepam, bromazepam, midazolam, diazepam, medazepam, and flurazepam over a wide range of concentrations. Analysis was performed with better precision, lower detection limits, and much more rapidly than by previously reported voltammetric techniques.The applicability of both procedures is discussed. The methods were applied to the analysis of commercially available tablets with minimum sample manipulation. The accuracy of the results was accessed by comparison with those obtained by use of the methods described in official pharmacopoeias. A critical comparison with those procedures is also presented.     

Single-ion approach to the susceptibility of an intermediate valence compound paramagnetic Imse

The magnetic properties of an intermediate valence compound are discussed within a single-ion framework. The effects of configuration mixing, crystalline electric fields, and external magnetic fields are included in the hamiltonian. The method incorporates in one single consistent approach both coherent (quantum) and incoherent (thermal) fluctuations. Numerical evaluation of the susceptibility and field dependent magnetization with parameters appropriate for TmSe yields results in good agreement with experiment.     

Dynamic kinetic resolution of atropisomeric amides

[reaction: see text] Using L-proline as catalyst in the asymmetric aldol reaction and a series of benzamides and naphthamides, we have accomplished a dynamic kinetic resolution that simultaneously establishes the stereochemistry of the atropisomeric amide's chiral axis and a stereogenic center. The enantioselectivities ranged from 82% to 95% and the diastereoselectivities from 2.1:1 to 7.0:1.