Controlled Release of the Anticancer Drug Cyclophosphamide from a Superparamagnetic ß-Cyclodextrin Nanosponge by Local Hyperthermia Generated by an Alternating Magnetic Field.

A ß-cyclodextrin (ß-CD) nanosponge (NS) was synthesized using diphenyl carbonate (DPC) as a cross-linker to encapsulate the antitumor drug cyclophosphamide (CYC), thus obtaining the NSs-CYC system. The formulation was then associated with magnetite nanoparticles (MNPs) to develop the MNPs-NSs-CYC ternary system. The formulations mentioned above were characterized to confirm the deposition of the MNPs onto the organic matrix and that the superparamagnetic nature of the MNPs was preserved upon association. The association of the MNPs with the NSs-drug complex was confirmed through field emission scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering, ζ-potential, atomic absorption spectroscopy, X-ray powder diffraction, selected area electron diffraction, and vibrating-sample magnetometer. The superparamagnetic properties of the ternary system allowed the release of CYC by utilizing magnetic hyperthermia upon the exposure of an alternating magnetic field (AMF). The drug release experiments were carried out at different frequencies and intensities of the magnetic field, complying with the "Atkinson-Brezovich criterion". The assays in AMF showed the feasibility of release by controlling hyperthermia of the drug, finding that the most efficient conditions were F = 280 kHz, H = 15 mT, and a concentration of MNPs of 5 mg/mL. CYC release was temperature-dependent, facilitated by local heat generation through magnetic hyperthermia. This phenomenon was confirmed by DFT calculations. Furthermore, the ternary systems outperformed the formulations without MNPs regarding the amount of released drug. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays demonstrated that including CYC within the magnetic NS cavities reduced the effects on mitochondrial activity compared to those observed with the free drug. Finally, the magnetic hyperthermia assays showed that the tertiary system allows the generation of apoptosis in HeLa cells, demonstrating that the MNPs embedded maintain their properties to generate hyperthermia. These results suggest that using NSs associated with MNPs could be a potential tool for a controlled drug delivery in tumor therapy since the materials are efficient and potentially nontoxic.

Conformational Changes of Poly(Maleic Anhydride-alt-styrene) Modified with Amino Acids in an Aqueous Medium and Their Effect on Cytocompatibility and Hemolytic Response.

The conformational changes of poly(maleic anhydride-alt-styrene) (PSMA) modified with different amino acids (PSMA-Aa) were studied in an aqueous medium as a function of ionic strength and pH. The specific viscosity of PSMA-Aa decreased with increasing salt concentration due to a more compact conformation. There was a decrease in surface tension with increasing concentrations of the modified polyelectrolyte having a greater effect for the PSMA modified with l-phenylalanine at pH 7.0, demonstrating a greater surface-active character. The conformational changes were also confirmed by molecular dynamics studies, indicating that PSMA-Aa exhibits a compact structure at pH 4.0 and a more extended structure at pH 7.0. On the other hand, the conformational changes of PSMA-Aa were related to its biological response, where the higher surface-active character of the PSMA modified with l-phenylalanine correlates very well with the higher hemolytic activity observed in red blood cells, in which the surface-active capacity supports lytic potency in erythrocytes. The cytocompatibility assays indicated that there were no significant cytotoxic effects of the PSMA-Aa. Additionally, in solvent-accessible surface area studies, it was shown that the carboxylate groups of the PSMA modified with l-phenylalanine are more exposed to the solvent at pH 7.0 and high salt concentrations, which correlates with lower fluorescence intensity, reflecting a loss of mitochondrial membrane potential. It is concluded that the study of the conformational changes in PE modified with amino acids is essential for their use as biomaterials and relevant to understanding the possible effects of PE modified with amino acids in biological systems.

Determination of Se(IV) concentration via cathodic stripping voltammetry in the presence of Cu(II) ions and ammonium diethyl dithiophosphate.

The development of a methodology for the determination of Se(IV) concentration via cathodic stripping voltammetry is described in this work. The methodology is based on the formation of copper selenide (Cu2Se), whose reduction signal at -0.60 V has been used as an analytical response to quantify the Se(IV) concentration in solution. The novelty of our methodology is the study of this system in the presence of a ligand such as ammonium diethyl dithiophosphate (ADTTP), which forms complexes with Cu(II) and Se(IV). The results showed that the presence of ADTTP plays an important role, increasing the sensitivity of the determination by almost a factor of two compared with the methodology in the absence of the ligand. The optimized conditions were pH 1.6 (phosphoric acid, 2.0 × 10-2 mol L-1), CCu(II) = 1.5 mg L-1, CADTTP = 2.0 µmol L-1, Eacc = -0.40 V and tacc = 45 s. The detection and the quantification limits obtained were 0.065 and 0.21 µg L-1, respectively, and linearity was maintained up to 4.0 µg L-1 of Se(IV). The sensitivity was 10.26 nA L µg-1. On the other hand, the relative standard deviation for 15 replicate measurements at 1.0 µg L-1 of Se(IV) was 1.6%. The usefulness of the method was evaluated by determining Se(IV) in two certified reference materials (TMDW and TM-28.4) with relative errors of less than 2.0%. The proposed method was successfully applied to the determination of Se(IV) in spiked tap water and in a liquid pharmaceutical formulation with satisfactory results. The developed methodology presents a low detection limit, good repeatability, selectivity and linear range. Furthermore, the sensibility of the method was achieved by applying a short accumulation time (45 s).

Determination of Sudan I in drinks containing Sunset yellow by adsorptive stripping voltammetry.

An efficient, fast and sensitive method for the determination of Sudan I (SI) in drinks containing Sunset yellow (Sy) is developed and validated using an adsorptive stripping voltammetric procedure. Sy is currently added to a large number of foods; however during their synthesis SI may be produced. The determination is based on adsorption of Sy and SI onto HMDE and later reduction of the azo group at -0.71 and -0.82V, respectively. Using the best set of the experimental conditions (pH 12.3; Eads: -0.40V) for the determination of SI in Sy, a linear response for SI in the concentration range 0.5-27.2µgL(-1) was found, with a detection limit of 1.5µgL(-1) in a tads of only 30s. The method was applied to the determination of SI in commercial drinks with satisfactory results. The presence of SI was confirmed by mass spectrometry.

Determination of Sb(III) using an ex-situ bismuth screen-printed carbon electrode by adsorptive stripping voltammetry.

The determination of Sb(III) on an ex-situ bismuth screen-printed carbon electrode (ex-situ BiSPCE) by means of adsorptive stripping voltammetry (AdSV) using quercetin-5'-sulfonic acid as chelating agent was optimized. The effect of different experimental parameters such pH, ligand concentration (CQSA), accumulation potential (Eacc) and accumulation time (tacc) were studied to obtain a wide linear range, the highest sensitivity and the lowest detection limit. Ex-situ BiSPCE was analytically compared with a sputtered bismuth screen-printed electrode (BispSPE) under optimal conditions. The obtained analytical parameters suggest that ex-situ BiSPCE behaves much better than BispSPE and the first was selected for this study. Optimal parameters were pH=4.6; CQSA=10.0 to 20.0×10(-6)molL(-1); Eacc=-0.5V and tacc=60s. Peak area is proportional to Sb(III) concentration up to 100.0µgL(-1) (tacc 60s) and 45.0µgL(-1) (tacc 120s) range, with detection limits of 1.2µgL(-)(1) (tacc 60s) and 0.8µgL(-1) (tacc 120s). The relative standard deviation for a Sb(III) solution (20.0µgL(-1)) was 3.9% for ten successive assays. Thus, the effect of various interfering metal ions was studied and the methodology was validated using a spiked groundwater reference material with very satisfactory results.