Long-term sustained-released in situ gels of a water-insoluble drug amphotericin B for mycotic arthritis intra-articular administration: preparation,in vitro and in vivo evaluation

Amphotericin B (AMB) was often used in intra-articular injection administration for fungal arthritis, because it could often bring a satisfactory therapeutic efficacy and a minimum systemic toxic side effect. However, because of the multiple operations and the frequent injections, the compliance of the patients was bad. Therefore, to develop a long-term sustained-released preparation of AMB for mycotic arthritis intra-articular administration is of great significance. The purpose of present study was to develop a long-term sustained-released in situ gel of a water-insoluble drug AMB for mycotic arthritis intra-articular administration. Based on the evaluations of the in vitro properties of the formulations, the formulation containing 10% (w/w) ethanol, 15% (w/w) PG, 0.75% (w/w) HA, 5% (w/w) purified soybean oil, 0.03% (w/w) α-tocopherol, 15% (w/w) water and 55% (w/w) glyceryl monooleate was selected as a suitable intra-articular injectable in situ gel drug delivery system for water-insoluble drug AMB. Furthermore, the results of the in vivo study on rabbits showed that the selected formulation was a safe and effective long-term sustained-released intra-articular injectable AMB preparation. Therefore, the presented in situ AMB gel could reduce the frequency of the administration in the AMB treatment of fungal arthritis, and then would get a good patient compliance.     

毒品滥用流行病模型的稳定性分析

现有毒品滥用流行病模型假设吸毒者康复后对毒品拥有永久"免疫"力，而忽视了其再次成为毒品易感者的可能性。针对这一问题，通过考虑社区治疗和隔离治疗两种措施，分析了毒品滥用人群的演化过程，提出了基于暂时"免疫"力的毒品滥用流行病模型，并计算了模型的基本再生数，讨论了模型平衡点的存在性和稳定性。当基本再生数小于1时，模型存在一个局部渐进稳定的无毒平衡点；当基本再生数大于1时，模型存在唯一的地方病平衡点，并利用几何方法证明了地方病平衡点的全局稳定性；当基本再生数等于1时，如果满足一定条件，模型出现后向分支现象。数值模拟验证了上述所有结果。研究结果表明提高隔离治疗率、改善社区治疗效果和降低接触传染率可以有效抑制毒品滥用的流行。     

In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

Elucidation of colour development and microstructural characteristics of Allium sativum fumigated with acetic acid

It has been well known that the greening of Allium sativum cloves could be formed after immersed in acetic acid solution. Nonetheless, no investigation was reported on colour development of A. sativum in response to acetic acid vapour until now. In this study, the brief exposure of A. sativum to acetic acid vapour (200–400 ppm) was combined with controlled atmosphere (5%, 20% and 80% CO₂) packaging storage to break cell membrane and green garlic. The garlic bulbs were fumigated with acetic acid before controlled CO₂ atmosphere packaging for 25 days at 4 °C. Fumigation with 200 ppm acetic acid followed by high CO₂ atmosphere packaging (80% CO₂) facilitated the garlic greening. It was also verified that γ‐glutamyl transpeptidase was involved in garlic greening in present study, and the compromise of glacial acetic acid vapour fumigation and CO₂ gas atmosphere in package stored at low temperature could result in garlic greening as well.     

Application of chitosan–alginate microspheres for the sustained release of bacteriophage in simulated gastrointestinal conditions

This study was designed to evaluate the acid stability, release property and antimicrobial efficacy of Escherichia coli O157:H7 bacteriophages encapsulated in chitosan–alginate microspheres under the simulated gastrointestinal conditions. The bacteriophages belonging to Myoviridae family were stable at the pH above 4 in trypticase soy broth. The chitosan–alginate microspheres exhibited protective effect on the viability of bacteriophages in the simulated gastric conditions at pH 2.0 and pH 2.5, showing 4.8 and 5.6 log PFU mL^‐1, respectively, after 1 h of incubation at 37 °C. The release per cent of bacteriophages from microspheres gradually increased up to 65% in the simulated intestinal condition (pH 7.5) at 37 °C for 6 h. The lytic efficacy of chitosan‐ and alginate‐encapsulated bacteriophages against E. coli O157:H7 was significantly maintained in the simulated intestinal conditions to 10 h of incubation (1.3 log reduction). The results suggest that the chitosan–alginate microspheres can be used as a reliable delivery system for bacteriophages.     

Multicellular Tumor Spheroids (MCTS) as a 3D In Vitro Evaluation Tool of Nanoparticles

Multicellular tumor spheroid models (MCTS) are often coined as 3D in vitro models that can mimic the microenvironment of tissues. MCTS have gained increasing interest in the nano‐biotechnology field as they can provide easily accessible information on the performance of nanoparticles without using animal models. Considering that many countries have put restrictions on animals testing, which will only tighten in the future as seen by the recent developments in the Netherlands, 3D models will become an even more valuable tool. Here, an overview on MCTS is provided, focusing on their use in cancer research as most nanoparticles are tested in MCTS for treatment of primary tumors. Thereafter, various types of nanoparticles—from self‐assembled block copolymers to inorganic nanoparticles, are discussed. A range of physicochemical parameters including the size, shape, surface chemistry, ligands attachment, stability, and stiffness are found to influence nanoparticles in MCTS. Some of these studies are complemented by animal studies confirming that lessons from MCTS can in part predict the behaviour in vivo. In summary, MCTS are suitable models to gain additional information on nanoparticles. While not being able to replace in vivo studies, they can bridge the gap between traditional 2D in vitro studies and in vivo models.     

龙潭水电站励磁装置可控硅易损原因及改进措施

通过龙潭水电站对励磁装置可控硅元件实施过电压保护改进前后实际效果的分析,介绍了一种有效的过压保护方式.     

High temperature controlled atmosphere experiments for catalysts in a transmission electron microscope

A new transmission electron microscopy (TEM) specimen preparation procedure for high temperature experiments using a controlled atmosphere specimen holder (HTCASH) has been developed. It is designed for studying the microstructure of catalyst specimens before and after treatments in various gases. The procedure involved (1) finding a new formula for the embedding material, (2) devising a new method of making specimen supports, and (3) developing a method for removing the embedding material after the specimen has been microtomed. These techniques were then brought together to produce the ideal specimens for the HTCASH experiments. As an extra benefit, this procedure is also suitable for preparing specimens for ultrahigh resolution imaging experiments. The application of the new procedure in HTCASH experiments is illustrated through a high temperature reduction of a Co/SiO₂-923 catalyst.     

Preparation and characterization of chitosan‐based dispersions

Complexation of chitosan in aqueous solutions by low molecular weight electrolytes is one of the simplest methods for the preparation of aqueous chitosan dispersions. In this work, the influence of storage time, sulfate concentration, method of preparation and surfactant content on some properties of the resultant chitosan dispersions (turbidity, viscosity and zeta potential) was analyzed. Turbidimetry was adequate to monitor the formation of particles, while viscometry was suitable to monitor changes in the dispersing phase. An analysis of the properties of these systems, mainly in terms of particle–particle and macromolecule–macromolecule interactions was carried out. Copyright © 2004 Society of Chemical Industry