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.     

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.     

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.     

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     

Rheological and drug‐release behaviour of a scleroglucan gel matrix at different drug loadings

The aim of this study was to investigate the drug‐loading effects on release and mechanical properties of a scleroglucan gel, with the intention of considering them in delivery systems formulations. The rheological and kinetic properties of a 2 % w/w scleroglucan gel matrix loaded with 0, 0.02, 0.04, 0.06, 0.2 and 0.4 % w/w of theophylline (Th, used as a model drug) were investigated. Rheological measurements were performed in a controlled‐stress rotational‐shear rheometer under isothermal conditions. For theophylline release from the gel a flat Franz cell was used and the kinetic parameters were derived applying a semi‐empirical power law. The influence of scleroglucan molar weight on kinetic and rheological behaviour was also studied. Results suggest two possible effects of drug loading on the gel network: in the 0.04–0.06 % w/w Th range a plasticizing effect and in the 0.2–0.4 % w/w Th range a rigidization effect. In the first range mentioned, the changes in the gel structural properties tested by means of rheological measurements are coincident with changes in drug‐release kinetics. Copyright © 2005 Society of Chemical Industry     

交联透明质酸的降解及其释药性能

用己二酸二酰肼（ADH）对透明质酸（HA）进行化学修饰，制备交联透明质酸（HA-ADH）薄膜。粘度法测试表明HA-ADH是一种可降解的生物材料，并且与HA相比，HA．ADH的降解速率减慢。在此基础上，研究了以疏水性的替硝唑（TDZ）和亲水性的头孢唑啉钠（CEZ）为模拟药物的HA-ADH药物载体薄膜的释药性能。紫外-可见（UV-Vis）吸收光谱检测表明，HA-ADH是一种疏水性药物TDZ的优良缓释制荆，这是由于TDZ的疏水性和HA-ADH薄膜的缓慢溶胀和降解性能的结合而得到的，药物的释放主要受扩散机制控制。     

Advancing controlled release packaging through smart blending

Researchers from Rutgers University and Clemson University have collaborated to develop a concept of using smart blending to generate functional packaging films for the controlled release of active compounds such as antimicrobials, antioxidants and flavour compounds to extend the shelf‐life of food. In this paper, literature results are reviewed to justify the significance of controlled release packaging (CRP) and the research gaps for further development are identified. A major research gap is the lack of packaging materials that can provide the release of active compounds at rates suitable for a wide range of food packaging applications. Smart blending is a promising technology for bridging this research gap. To fully realize the potentials of smart blending, a systematic approach for developing CRP using smart blending is also presented. Copyright © 2005 John Wiley & Sons, Ltd.     

Temperature effects on the mass flow rate in the SBI and similar heat‐release rate test equipment

In various medium‐to‐large‐scale fire test equipments like the ISO room corner test (RC), and more recently, the single burning item test (SBI) the mass flow rate measurement of the combustion gases plays a key role in the determination of the heat‐release rate and smoke‐production rate. With the knowledge of the velocity profile and the temperature of the flow, the mass flow rate is obtained by measuring the velocity on the axis of the duct. This is done by means of a bi‐directional probe based on the pitot principle. However, due to the variation of the mean temperature and the temperature gradient in any cross section of the duct, introduced by ever changing combustion gas temperatures, the velocity nor the density profile are constant in time. This paper examines the resulting uncertainty on the mass flow rate. Copyright © 2006 John Wiley & Sons, Ltd.