Role of Microstructure in Drug Release from Chitosan Amorphous Solid Dispersions

The unexpected dissolution behaviour of amorphous diflunisal-chitosan solid dispersions (kneading method) with respect to the crystalline co-evaporated systems is the starting point of this research. This work is an in-depth study of the diflunisal release behaviour from either chitosan or carboxymethylchitosan dispersions. The microstructure is not usually considered when designing this type of products; however, it is essential to understand the process of solvent penetration and subsequent drug release through a polymeric system, as has been evidenced in this study. In accordance with the kinetic data analysed, it is possible to conclude that the porous structure, conditioned by the sample preparation method, can be considered the main factor involved in diflunisal release. The low mean pore size (1–2 μm), low porosity, and high tortuosity of the amorphous kneaded products are responsible for the slow drug release in comparison with the crystalline coevaporated systems, which exhibit larger pore size (8–10 μm) and lower tortuosity. Nevertheless, all diflunisal-carboxymethylchitosan products show similar porous microstructure and overlapping dissolution profiles. The drug release mechanisms obtained can also be related to the porous structure. Fickian diffusion was the main mechanism involved in drug release from chitosan, whereas an important contribution of erosion was detected for carboxymethylchitosan systems, probably due to its high solubility.     

Photoinduced Heterogeneous Processes on Chemical Phase Components of Solid Tropospheric Aerosols

This work shows the results of photoinduced process investigations over some metal oxides of the semiconductor type (In₂O₃, Sc₂O₃, V₂O₅ and MoO₃) and insulator type (MgO). These metal oxides can be the chemical phase components of solid tropospheric aerosols. The quantum yields and spectral dependencies of the quantum yields of photoadsorption and photocatalytic oxidation in the spectral region including the spectral region of solar tropospheric irradiation are determined.     

CaO–ZrO2 Solid Solution: A Highly Stable Catalyst for the Synthesis of Dimethyl Carbonate from Propylene Carbonate and Methanol

CaO–ZrO₂ prepared by co-precipitation showed to be a well-performed catalyst for the transesterification of propylene carbonate (PC) and methanol. The characterization by X-ray powered diffraction (XRD) and Raman spectroscopy indicated that CaO was doped into the lattice of ZrO₂ to form CaO–ZrO₂ solid solution. Such a solid solution was a strong solid base, which was proved by CO₂ temperature program desorption (CO₂-TPD). As a result, the catalyst showed high stability towards the transesterification of propylene carbonate and methanol into dimethyl carbonate with high PC conversion, especially being subjected to the continuous production of dimethyl carbonate at reactive distillation reactor for 250 h without any obvious loss of activity at the PC conversion of 95%.     

The pH-Dependent Controlled Release of Encapsulated Vitamin B1 from Liposomal Nanocarrier

In this work, we firstly presented a simple encapsulation method to prepare thiamine hydrochloride (vitamin B₁)-loaded asolectin-based liposomes with average hydrodynamic diameter of ca. 225 and 245 nm under physiological and acidic conditions, respectively. In addition to the optimization of the sonication and magnetic stirring times used for size regulation, the effect of the concentrations of both asolectin carrier and initial vitamin B₁ on the entrapment efficiency (EE %) was also investigated. Thermoanalytical measurements clearly demonstrated that after the successful encapsulation, only weak interactions were discovered between the carriers and the drug molecules. Moreover, the dissolution profiles under physiological (pH = 7.40) and gastric conditions (pH = 1.50) were also registered and the release profiles of our liposomal B₁ system were compared with the dissolution profile of the pure drug solution and a manufactured tablet containing thiamin hydrochloride as active ingredient. The release curves were evaluated by nonlinear fitting of six different kinetic models. The best goodness of fit, where the correlation coefficients in the case of all three systems were larger than 0.98, was reached by application of the well-known second-order kinetic model. Based on the evaluation, it was estimated that our liposomal nanocarrier system shows 4.5-fold and 1.5-fold larger drug retention compared to the unpackaged vitamin B₁ under physiological conditions and in artificial gastric juice, respectively.     

用DSC研究3,3-偕二氟氨甲基氧杂环丁烷与炸药和固体推进剂组分的化学相容性

按照GJB 772A-97 502.1法测量了该黏合剂单体3,3-偕二氟氨甲基氧杂环丁烷(BDFAO)与典型单质炸药、推进剂组分的化学相容性。结果表明,BDFAO与RDX、HMX、LLM-105、AP、碱式碳酸铅的化学相容性达到1级,与DNTF、HNS、B、1号中定剂的化学相容性达到2级,BDFAO与TNT、NC-NG、Al化学不相容。     

A Molecular and Chemical Perspective in Defining Melatonin Receptor Subtype Selectivity

Melatonin is primarily synthesized and secreted by the pineal gland during darkness in a normal diurnal cycle. In addition to its intrinsic antioxidant property, the neurohormone has renowned regulatory roles in the control of circadian rhythm and exerts its physiological actions primarily by interacting with the G protein-coupled MT₁ and MT₂ transmembrane receptors. The two melatonin receptor subtypes display identical ligand binding characteristics and mediate a myriad of signaling pathways, including adenylyl cyclase inhibition, phospholipase C stimulation and the regulation of other effector molecules. Both MT₁ and MT₂ receptors are widely expressed in the central nervous system as well as many peripheral tissues, but each receptor subtype can be linked to specific functional responses at the target tissue. Given the broad therapeutic implications of melatonin receptors in chronobiology, immunomodulation, endocrine regulation, reproductive functions and cancer development, drug discovery and development programs have been directed at identifying chemical molecules that bind to the two melatonin receptor subtypes. However, all of the melatoninergics in the market act on both subtypes of melatonin receptors without significant selectivity. To facilitate the design and development of novel therapeutic agents, it is necessary to understand the intrinsic differences between MT₁ and MT₂ that determine ligand binding, functional efficacy, and signaling specificity. This review summarizes our current knowledge in differentiating MT₁ and MT₂ receptors and their signaling capacities. The use of homology modeling in the mapping of the ligand-binding pocket will be described. Identification of conserved and distinct residues will be tremendously useful in the design of highly selective ligands.     

Comparative Study of Chemical Stability of a PK20 Opioid–Neurotensin Hybrid Peptide and Its Analogue [Ile9]PK20—The Effect of Isomerism of a Single Amino Acid

Chemical stability is one of the main problems during the discovery and development of potent drugs. When ignored, it may lead to unreliable biological and pharmacokinetics data, especially regarding the degradation of products’ possible toxicity. Recently, two biologically active drug candidates were presented that combine both opioid and neurotensin pharmacophores in one entity, thus generating a hybrid compound. Importantly, these chimeras are structurally similar except for an amino acid change at position 9 of the peptide chain. In fact, isoleucine (C₆H₁₃NO₂) was replaced with its isomer tert-leucine. These may further lead to various differences in hybrids’ behavior under specific conditions (temperature, UV, oxidative, acid/base environment). Therefore, the purpose of the study is to assess and compare the chemical stability of two hybrid peptides that differ in nature by way of one amino acid (tert-leucine vs. isoleucine). The obtained results indicate that, opposite to biological activity, the substitution of tert-leucine into isoleucine did not substantially influence the compound’s chemical stability. In fact, neither hydrolysis under alkaline and acidic conditions nor oxidative degradation resulted in spectacular differences between the two compounds—although the number of potential degradation products increased, particularly under acidic pH. However, such a modification significantly reduced the compound’s half-life from 204.4 h (for PK20 exposed to 1M HCl) to 117.7 h for [Ile⁹]PK20.     

Use of Raw and Acid-Treated MnO2 as Catalysts for Oxidation of Dyes in Water: A Case Study with Aqueous Methylene Blue

Catalytic wet oxidation has become one of the best options for mineralization of dyes in water. In this work, mineralization of methylene blue in water was tried by using raw and acid-treated (0.50, 0.75, and 1.00 N H₂SO₄) MnO₂ as oxidation catalysts. Fourier transform infrared, scanning electron microscopy, surface area and cation exchange capacity measurements were used to characterize the catalysts. The acid-treated materials showed large increases in surface area while changes in other surface characteristics were moderate in nature. The oxidative destruction of the dye was possible at near room temperature and the process was optimized with respect to interaction time, dye concentration, catalyst loading, pH of the medium, and temperature. The dye (1.0 mg/L) was oxidized to the extents of 88.5%, 96.5%, 96.8%, and 97.7% with corresponding chemical oxygen demand (COD) reduction of 64.7%, 86.4%, 87.2%, and 88.2% by raw MnO₂, 0.50, 0.75, and 1.00 N acid-treated MnO₂(catalyst loading 2.5 g/L), respectively. The reduction in COD indicated oxidation of the dye to simpler organic compounds achieving mineralization to a large extent. The oxidation followed first-order kinetics and the catalysts could be used up to six repeated runs without much change in activity. Analysis of the intermediate products of oxidation helped in proposing the potential pathways for oxidative conversion of methylene blue.     

Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D3 Analogues and Their Stability to hCYP24A1-Dependent Catabolism

Two 24-fluoro-25-hydroxyvitamin D₃ analogues (3,4) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D₃ side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24R)- and (24S)-24-fluoro-25-hydroxyvitamin D₃ revealed that the C24-R-configuration isomer 4 was more resistant to CYP24A1-dependent metabolism than its 24S-isomer 3. The new synthetic route of the CYP24A1 main metabolite (24R)-24,25-dihydroxyvitamin D₃ (6) and its 24S-isomer (5) was also studied using synthetic intermediates (30,31) in parallel.     

A Study of the Crystallization, Melting, and Foaming Behaviors of Polylactic Acid in Compressed CO2

The crystallization and melting behaviors of linear polylactic acid (PLA) treated by compressed CO₂ was investigated. The isothermal crystallization test indicated that while PLA exhibited very low crystallization kinetics under atmospheric pressure, CO₂ exposure significantly increased PLA’s crystallization rate; a high crystallinity of 16.5% was achieved after CO₂ treatment for only 1 min at 100 °C and 6.89 MPa. One melting peak could be found in the DSC curve, and this exhibited a slight dependency on treatment times, temperatures, and pressures. PLA samples tended to foam during the gas release process, and a foaming window as a function of time and temperature was established. Based on the foaming window, crystallinity, and cell morphology, it was found that foaming clearly reduced the needed time for PLA’s crystallization equilibrium.     

Nonisothermal Crystallization Modeling and Simulation of Polypropylene/Nano Ca3(PO4)2 Composites with Variation in Wt.% of Loading and Reduction in Nanosize

Nonisothermal crystallization kinetics of polypropylene (PP)/Ca₃(PO₄)₂ composites was studied using differential scanning calorimetry (DSC) for various nanosizes by employing Avrami and Ozawa's combined analysis. Parameters such as Avrami's exponent (n) and composite growth rate constant (Z_t) were determined, which characterize the system of different nanosize composites and virgin PP. The relative degree of crystallinity as a function of temperature for PP-nano Ca₃(PO₄)₂ composites at the same cooling rate and sigmoidal shape of curves indicates that there is a strong interaction between PP molecule and nanolayer, which leads to greater nucleation with reduction in nanosizes. A theoretical combination of kinetic equations is found to be suitable to describe the physical phenomena of a real system. The values of parameters n, Z_t, and predicted time t for crystallization at a single cooling rate were obtained from the mathematical model.     

Electrochemical activity, stability and degradation characteristics of IrO2-based electrodes in aqueous solutions containing C1 compounds

In this paper, we investigate the electrocatalytic behavior and degradation characteristics of IrO₂-based electrodes in Na₂SO₄ solutions containing C₁ compounds (CH₃OH, HCHO and HCOOH). Decreases are generally observed in the electrochemically active area, electrochemical stability and durability of the electrodes in aqueous solutions in the presence of these organic substrates. The following sequence holds for the influence of C₁ compounds on the electrode properties (i.e. activity and stability): CH₃OH > HCHO > HCOOH. The corrosion characteristics of electrode are studied by X-ray diffraction measurements. For the first time, the decomposition and dissolution of active oxide layers are quantitatively characterized from the decreases in cell volume of rutile-structured IrO₂ crystallite and from the increases in texture coefficient of (0 0 2) planes, respectively, as a result of the accelerated lifetime tests.     

Supercritical CO2 as an efficient medium for layered silicate organomodification: Preparation of thermally stable organoclays and dispersion in polyamide 6

In this study, the preparation of organoclays via a new process using supercritical carbon dioxide is described. This method turns out to be very efficient with various surfactants, in particular nonwater-soluble alkylphosphonium salts. The influence of the surfactant as well as of the clay nature on the thermal stability of the organoclay is evaluated by thermogravimetric analysis. Phosphonium-based montmorillonites are up to 90 °C more stable than ammonium-based montmorillonites. Moreover, the use of hectorite adds another 40 °C of thermal stability to the phosphonium-modified clays. These organomodified clays have been melt-blended with polyamide 6 and morphology as well as fire properties of the nanocomposites are discussed, in terms of influence of the stability of organoclays. For the first time, comparison of nanocomposites based on clay organomodified by ammonium and phosphonium salts of the very same structure is reported.     

The Ability of Chlorophyll to Trap Carcinogen Aflatoxin B1: A Theoretical Approach

The coordination of one and two aflatoxin B₁ (AFB₁, a potent carcinogen) molecules with chlorophyll a (chl a) was studied at a theoretical level. Calculations were performed using the M06-2X method in conjunction with the 6-311G(d,p) basis set, in both gas and water phases. The molecular electrostatic potential map shows the chemical activity of various sites of the AFB₁ and chl a molecules. The energy difference between molecular orbitals of AFB₁ and chl a allowed for the establishment of an intermolecular interaction. A charge transfer from AFB₁ to the central cation of chl a was shown. The energies of the optimized structures for chl a show two configurations, unfolded and folded, with a difference of 15.41 kcal/mol. Chl a appeared axially coordinated to the plane (α-down or β-up) of the porphyrin moiety, either with the oxygen atom of the ketonic group, or with the oxygen atom of the lactone moiety of AFB₁. The complexes of maximum stability were chl a 1-α-E-AFB₁ and chl a 2-β-E-AFB₁, at −36.4 and −39.2 kcal/mol, respectively. Additionally, with two AFB₁ molecules were chl a 1-D-2AFB₁ and chl a 2-E-2AFB₁, at −60.0 and −64.8 kcal/mol, respectively. Finally, biosorbents containing chlorophyll could improve AFB₁ adsorption.     

Structure Characteristics and NO Selective Catalytic Reduction Property of Sn x Zr1-x O2 Solid Solution Catalysts

Novel catalysts, Sn_xZr_1-xO₂ solid solutions, for NO selective catalytic reduction:NO SCR) are reported. They have much higher activity and selectivity than SnO₂ and ZrO₂. Sn⁴⁺ is the main reductive sites as proved by TPR. The dilution of Sn sites by the coexisting Zr causes a suppression of propene combustion and consequently promoted the selective reduction of NO. The rutile structure might be beneficial to NO SCR.     

Electrochemical reduction of 2,4-dinitrophenol on nanocomposite electrodes modified with mesoporous silica and poly(vitamin B1) films

Electrochemical reduction of 2,4-dinitrophenol was investigated on a glassy carbon electrode modified with a nanocomposite Santa Barbara Amorphous silica (SBA-15) film and poly(vitamin B₁) film. For sensitive and selective detections, vanadium pentoxide and cerium oxide nanoparticles were incorporated into the matrix of SBA-15. 2,4-Dinitrophenol was reduced on the modified electrode at −0.39 and −0.25 V, corresponding to the reduction of 4-dinitrophenol and 2-dinitrophenol, respectively. Both cathodic peak currents were controlled by the diffusion of 2,4-dinitrophenol. The amplitude of the peak currents was proportional to the 2,4-dinitrophenol concentration in the range of 3.0–30 μM. The modified electrode demonstrated a long lifetime for the detection of 2,4-dinitrophenol. The detection limit of 2,4-dinitrophenol was 0.5 μM. Moreover, the modified electrode was used successfully to detect 2,4-dinitrophenol in lake water.     

The Effect of Ozone on Aflatoxin M1, Oxidative Stability,Carotenoid Content and the Microbial Count of Milk

In the current investigation, attempts were made to determine if ozone treatment can affect the aflatoxin M₁ (AFM₁) content of milk. Aflatoxin M₁ by a pre-determined concentration of 0.56 μg/Kg was added to milk. Milk samples, were then exposed to gaseous ozone (80 mg/min) in containers for durations of 0, 0.5, 1, 2, 5 and 10 min. The longer exposure time to ozone was more efficient in breaking down the AFM₁ in milk. Results indicated that AFM₁ was reduced by 50%, when milk was ozonated at for 5 min. The pH and oxidation value of milk did not change significanty as a result of the treatments. The β-carotene content was significantly reduced and the total microbial count in milk decreased parallel to the longer exposure time. Also, it was through this longer exposure time by ozone that the L* values of milk increased significantly (p < 0.05), while the b* values significantly decreased. To the best of our knowledge, this is the first study that uses ozone to degrade AFM₁ in milk.