Dispersion, fractionation and characterization of sub-100nm P25 TiO2 nanoparticles in aqueous media

Despite of the widespread use of manufactured nanomaterials and increasing concerns on their potential risk, only limited information is available on their physicochemical properties in toxicologically relavant aqueous media. Here, P25 TiO₂ (Evonik GmbH), one of the well-known and widely-used photocatalytic TiO₂, was dispersed and fractionated in aqueous media, and its physicochemical properties, especially for its sub-100 nm fraction, was carefullly studied. The colloidal properties of TiO₂ nanoparticles, such as ag]glomeration and sedimentation, were found strongly dependent on the physicochemical characteristics of nanoparticles (e.g., hydrodynamic size distribution, type of capping ligands and surface charge) as well as those of the aqueous media used (e.g., ionic strength and chemical compositions). This study has shown the importance of standardized dispersion and characterization protocol for toxicity tests, which is urgently needed for reliable, reproducible and impartial toxicity tests of manufactured nanomaterials.     

Skin absorption potential of ZnO nanoparticles

In spite of widely use of zinc oxide (ZnO) nanoparticles (NPs) in cosmetic industry and in our daily lives, there are insufficient data on their potential of skin absorption. This study was conducted to investigate the potential of skin absorption induced by ZnO NPs, especially influences of the surface charge and different particle size. Assessment of potential of skin absorption was estimated using 3D EpiDerm? model (EPI-200) as human skin equivalent model (HSEM). This study demonstrated no evidence of significant penetration of ZnO NPs into the HSEM after 24 h exposure.     

Toxicity of ZnO nanoparticles in healthy adult mice

In this study, we extended previous work to evaluate the oral toxicity of ZnO nanoparticles and their possible effects on different serum-elements and sexual hormones in the mouse. The histopathological changes have also been examined. Significant recorded increases in alanine aminotransferase and aspartate aminotransferase activity in all mice exposed to ZnO nanoparticles suggest that these nanoparticles can cause hepatic injury. Hepatocyte necrosis and other pathological observations also confirmed liver damage. Moreover, Glomeruli segmentation, hydropic degeneration in epithelial cells, necrosis of epithelial cells in tubules and swelling in epithelial cells of proximal tubules were found in all kidney tissues, which demonstrated that ZnO nanoparticles have severe toxicological effects on kidney. Serous inflammation, severe hyperemia in alveoli, and edema were observed as pathological findings in the lung which suggest that the lung is the third target tissue of the ZnO nanoparticles.     

Degradation of carmustine in aqueous media.

The degradation rate of carmustine was investigated in buffered aqueous media at several pH values. The buffering agents studied were those with potential use in parenteral formulations of this drug: acetate, citrate, and phosphate. The apparent first-order degradation rate constants were calculated using a linear regression procedure. A pH range over which minimum degradation occurred was ascertained. General acid and specific base catalysis was demonstrated for the degradation of carmustine. From the data at 5, 22, and 37 degrees, the apparent activation energies for carmustine degradation in buffered aqueous media were computed and were strongly pH dependent.     

In vitro erythemal UV-A protection factors of inorganic sunscreens distributed in aqueous media using carnauba wax-decyl oleate nanoparticles.

This paper describes the in vitro photoprotection in the UV-A range, i.e. 320-400 nm obtained by the use of carnauba wax-decyl oleate nanoparticles either as encapsulation systems or as accompanying vehicles for inorganic sunscreens such as barium sulfate, strontium carbonate and titanium dioxide. Lipid-free inorganic sunscreen nanosuspensions, inorganic sunscreen-free wax-oil nanoparticle suspensions and wax-oil nanoparticle suspensions containing inorganic sunscreens dispersed either in their oil phase or their aqueous phase were prepared by high pressure homogenization. The in vitro erythemal UV-A protection factors (EUV-A PFs) of the nanosuspensions were calculated by means of a sun protection analyzer. EUV-A PFs being no higher than 4 were obtained by the encapsulation of barium sulfate and strontium carbonate, meanwhile by the distribution of titanium dioxide in presence of wax-oil nanoparticles, the EUV-A PFs varied between 2 and 19. The increase in the EUV-A PFs of the titanium dioxide obtained by the use of wax-oil nanoparticles demonstrated a better performance of the sun protection properties of this pigment in the UV-A region.     

高乌甲素纳米粒的制备及其在大鼠体内药动学

目的:制备可持续释放且能治疗疼痛的载高乌甲素(LA)的聚乳酸(PLA)纳米粒,并考察其体外释药情况和在大鼠体内的药动学特性。方法:采用O/W乳化-溶剂挥发法制备载高乌甲素的聚乳酸纳米粒(LA/PLA NPs),运用激光粒度仪测定其粒径,原子力显微镜观察其形貌,动态透析法考察其体外释药特性,反相高效液相色谱法(RP-HPLC)测定血药浓度,PKSolver程序处理药-时数据,并以LA为参比进行大鼠腹腔注射的药动学研究。结果:LA/PLA NPs外观呈圆形或类圆形,大小均匀,平均粒径(429±9.19)nm,包封率(86.34±2.15)%、载药量(45.85±1.34)%,体外可持续缓慢释放15 d,体内可释药8 d以上,其主要药动学参数为:t_1/2=(103.16±21.57)h,t_max=(3.6±1.34) h,C_max=(3.50±0.69)μg·mL^-1,AUC_(0-t)=(455.14±26.18) μg·mL^-1·h。结论:LA/PLA NPs制备工艺简单,重复性好,体内药-时过程符合非房室模型,具有良好的缓释效果。     

Effect of food dyes on radicals in aqueous media

The rates of reaction of photogenerated hydroperoxy and hydroxyl radicals on the photostability of aqueous solutions of dequalinium chloride irradiated with simulated sunlight at 38 ± 1°C have been investigated, with and without the addition of amaranth and quinoline yellow. These reactions follow second-order kinetics and the dyes tested markedly increase the rate constants of the reactions. Hydroperoxy radicals react with hydroxyl radicals preferentially to the dequalinium chloride resulting in lower reaction rate constants for the latter. Acetaldehyde was used as a scavenger of hydroperoxy radicals.     

Nortropacocaine hydrochloride conformation in aqueous and hydrophobic media.

The nortropacocaine hydrochloride PMR spectra in deuterium oxide and in deuterochloroform differed markedly. A detailed conformational analysis using vicinal 1H-1H coupling constants revealed the molecular conformation to be identical in both solvents. The preferred conformation was one in which the piperidine component existed as a deformed chair. The spectral differences were due to a decreased deshielding of the protonated nitrogen on the neighboring bicyclic ring protons, resulting in chemical shift changes.     

Unusual solubility behaviour of cyclosporin A in aqueous media.

The solubility of cyclosporin A was determined in water and in Sorensen buffers at pH 1.2 and 6.6 at temperatures ranging from 5 to 37 degrees C. No differences in solubility behaviour were observed among the three aqueous media. Solubility was found to be inversely proportional to the temperature in each medium, indicating that the heat of solution was exothermic in each case.     

Degradation kinetics of a substituted carbinolamine in aqueous media.

The apparent first-order breakdown of the medicinally active agent 3-(p-chlorophenyl)-2-ethyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazol-3-ol was studied in aqueous solutions where dehydration gave the unsaturated compound 3-(p-chlorophenyl)-5,6-dihydro-2-ethylimidazo[2,1-b]thiazole. This thiazole was the primary solvolytic product produced in approximately quantitative yields for the temperature range studied and ostensibly underwent no further reaction in acidic media even on prolonged heating. Investigations were carried out at various pH values in standard buffers at constant ionic strength. The ionization constants of the compounds are reported as well as the apparent activation energies for the degradation in acid and acetate buffers. The influence of ionic strength on the velocity constant was determined.     

Effect of cyclodextrins on anthracycline stability in acidic aqueous media

The effect of cyclodextrins on the stability of six anthracyclines in acidic medium at 50°C has been investigated using a stability-indicating high pressure liquid Chromatographic method. The influences of various parameters, such as the structure of cyclodextrins (-cyclodextrin, -cyclodextrin, dimethyl--cyclodextrin and -cyclodextrin) and anthracyclines, cyclodextrin concentration, the pH and the presence of a co-solvent, are investigated. Lineweaver-Burk plots were used to calculate the stability constants of the various inclusion complexes as well as the rate constants for degradation of the anthracycline guest molecules in the complexes with the host cyclodextrins. Anthracyclines complexate only with -cyclodextrin to a substantial extent. On complexation the stability of the guest molecule increases, however, the degradation pattern does not alter. The influence of the pH on the degradation of the included molecule is identical to that of the free drug. Addition of co-solvents, such as acetonitrile, causes decomposition of the complex.     

Catalysis in aqueous media for the synthesis of drug-like molecules

The design of straightforward and practical chemical syntheses that satisfy economic and ecological constraints is a major challenge in R&D. Ideally, a sustainable chemical synthesis should be safe, environmentally benign, reasonable in terms of cost, and careful in the use of resources and energy. The capability to develop synthetic strategies that meet these criteria is a priority in the manufacture of fine chemicals and pharmaceuticals, considering that the health and welfare of society increasingly depend on such industries. Among the various objectives to be pursued in sustainable manufacturing, this review focuses on two main goals: (i) the minimization of waste; and (ii) the replacement of toxic and volatile organic solvents with alternative, safer solvents - specifically water. In this context, the development of methods for catalysis in alternative reaction media is recognized as one of the most important approaches in modern chemical production.     

Titanium oxide shell coatings decrease the cytotoxicity of ZnO nanoparticles

Although nanozinc oxide (nano-ZnO) is applied widely in photocatalysts and gas sensors and in biological fields, it can cause serious oxidative stress and DNA damage to mammalian cells. Our aim in this study was to reduce the cytotoxicity of nano-ZnO by coating it with a TiO(2) layer. We used a sol-gel method to synthesize core (nano-ZnO)/shell (TiO(2)) nanoparticles (NPs) with various degrees of coating. Transmission electron microscopy and Raman spectroscopy confirmed that TiO(2) was coated on the nano-ZnO. Moreover, a decrease in the intensity of the pre-edge signal in Ti K-edge X-ray absorption near edge structure spectra revealed that the core/shell NPs had more Ti-O coordination than pure TiO(2) particles; in addition, the Zn K-edge extended X-ray absorption fine structure spectra revealed that after the ZnO NPs had been coated with TiO(2), the coordination number of the ZnO shell increased to 3.3 but that of the ZnZn shell decreased to 6.2, providing further evidence for the ZnO/TiO(2) core/shell structure. To ensure that the core/shell structures did indeed decrease the toxicity of nano-ZnO, we tested the effects of equal amounts of physical mixtures of ZnO and TiO(2) NPs for comparison, employing methyl tetrazolium (MTT), interleukin-8 (IL-8), lactate dehydrogenase (LDH), and 2',7'-dichlorofluorescin diacetate (DCFH-DA) to assess the particle-induced cytotoxicity, inflammatory response, membrane damage, and intercellular reactive oxygen species (ROS). From X-ray diffraction patterns, we identified the TiO(2) shell as having an amorphous phase, which, unfortunately, exhibited slight cytotoxicity toward the human lung epithelial cell line (A549). Nevertheless, our core/shell nanostructures exhibited less oxidative stress toward A549 cells than did their corresponding ZnO/TiO(2) physical mixtures. In addition, a greater coating of TiO(2) decreased the toxicity of the ZnO NPs. It appears that the ZnO/TiO(2) core/shell structure moderated the toxicity of nano-ZnO by curtailing the release of zinc ions and decreasing the contact area of the ZnO cores.     

Colloidal and thermal characteristics of concentrated dispersions of polymethacrylate-based latices for aqueous enteric coating

We have used rheological and thermal methods to study the colloidal characteristics of a widely used technical latex. The dispersions of poly(methacrylic acid-ethyl acrylate) (Eudragit L100-55) were found to be stabilized by a combination of electrostatic and steric mechanisms termed as electrosteric stabilization. The electrosteric stabilization is considered to arise in part from dissolved polymer chains with charged carboxylic groups extending out into the continuous phase. The presence of dissolved polymer chains in the dispersion implies that coalescence and interpenetration will be facilitated during film formation, enabling a smooth continuous film to be formed. The extent of the stabilization layer and an effective hard-sphere volume was estimated to discuss the steady shear and viscoelastic properties in this context. The glass transition temperature (Tg) of the particles making up the dispersion has also been determined as a function of sorbed moisture and modeled by the Gordon-Taylor equation modified for specific interaction between water, surfactant, and polymer. This parameter at high moisture content can be used as a first approximation to the minimum film-forming temperature (MFT). Change in Tg (and thus MFT) with moisture content implies that the coating process must be controlled so as to produce a rate of drying slow enough to allow coalescence to occur.     

塞来昔布固体脂质纳米粒的制备及其在大鼠体内的药动学

目的:制备塞来昔布固体脂质纳米粒,并考察大鼠灌胃给药后体内的药动学特征。方法:采用热熔乳化超声-低温固化法制备塞来昔布固体脂质纳米粒,并对制得的纳米粒进行表征。将12只Wistar大鼠随机分为为塞来昔布原料药组和塞来昔布固体脂质纳米粒组,灌胃给药剂量均为100 mg·kg^-1,采用高效液相色谱法测定大鼠血浆中塞来昔布的浓度,采用3P97程序计算塞来昔布药动学参数。结果:塞来昔布固体脂质纳米粒平均粒径为(183.6±44.5)nm,PdI为(0.217±0.052),Zeta电位为(-30.4±5.2)mV。塞来昔布原料药和塞来昔布固体脂质纳米粒在大鼠体内的AUC_(0-t)分别为(4.47±0.72)和(11.64±2.01)mg·L^-1·h;t_1/2分别为(13.45±1.89)和(10.12±1.24)h;t_max 分别为(2.33±0.21)和(1.31±0.14)h;C_max分别为(0.86±0.12)和(2.14±0.46 )mg·L^-1。结论:塞来昔布固体脂质纳米粒能够明显改善大鼠体内塞来昔布的药动学行为,与塞来昔布原料药相比具有明显的缓释效果,同时提高了药物的生物利用度。     

Determination of photostability and photodegradation products of indomethacin in aqueous media

Photochemical behaviour of indomethacin in aqueous media at 254 nm, 310 nm and sunlight was studied by HPLC. The drug exhibited a similar behaviour in all the irradiation experiments affording eight photoproducts that were separated and identified. The main photochemical routes are suggested to proceed via decarboxylation, followed by oxygenation to give an alcohol and an aldehyde and/or by solvent trapping to produce the alcohol. Photoinduced hydrolysis of CO-N bond and oxidative C2-C3 bond breakage also occur.