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 Tg of the polymeric caplet from the Tg'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. 相似文献
Although hyperhomocysteinemia (HHcy) elicits lower than normal body weights and skeletal muscle weakness, the mechanisms remain unclear. Despite the fact that HHcy-mediated enhancement in ROS and consequent damage to regulators of different cellular processes is relatively well established in other organs, the nature of such events is unknown in skeletal muscles. Previously, we reported that HHcy attenuation of PGC-1α and HIF-1α levels enhanced the likelihood of muscle atrophy and declined function after ischemia. In the current study, we examined muscle levels of homocysteine (Hcy) metabolizing enzymes, anti-oxidant capacity and focused on protein modifications that might compromise PGC-1α function during ischemic angiogenesis. Although skeletal muscles express the key enzyme (MTHFR) that participates in re-methylation of Hcy into methionine, lack of trans-sulfuration enzymes (CBS and CSE) make skeletal muscles more susceptible to the HHcy-induced myopathy. Our study indicates that elevated Hcy levels in the CBS−/+ mouse skeletal muscles caused diminished anti-oxidant capacity and contributed to enhanced total protein as well as PGC-1α specific nitrotyrosylation after ischemia. Furthermore, in the presence of NO donor SNP, either homocysteine (Hcy) or its cyclized version, Hcy thiolactone, not only increased PGC-1α specific protein nitrotyrosylation but also reduced its association with PPARγ in C2C12 cells. Altogether these results suggest that HHcy exerts its myopathic effects via reduction of the PGC-1/PPARγ axis after ischemia. 相似文献
Reactive oxygen species (ROS) refers to the reactive molecules and free radicals of oxygen generated as the by-products of aerobic respiration. Historically, ROS are known as stress markers that are linked to the response of immune cell against microbial invasion, but recent discoveries suggest their role as secondary messengers in signal transduction and cell cycle. Tissue engineering (TE) techniques have the capabilities to harness such properties of ROS for the effective regeneration of damaged tissues. TE employs stem cells and biomaterial matrix, to heal and regenerate injured tissue and organ. During regeneration, one of the constraints is the unavailability of oxygen as proper vasculature is absent at the injured site. This creates hypoxic conditions at the site of regeneration. Hence, effective response against the stresses like hypoxia spurs the regeneration process. Contrary, hyperoxic condition may increase the risk of ROS stress at the site. TE tries to overcome these limitations with the new class of biomaterials that can sense such stresses and respond accordingly. This review endeavors to explain the role of ROS in stem cell proliferation and differentiation, which is a key component in regeneration. This compilation also highlights the new class of biomaterials that can overcome the hypoxic conditions during tissue regeneration along with emphasis on the ROS-responsive biomaterials and their clinical applications. Incorporating these biomaterials in scaffolds development holds huge potential in tissue or organ regeneration and even in drug delivery.
Fire losses due to cable fire in thermal power plants and industrial units are mounting. Fire in cable galleries is caused either by an external source or internal heating due to overloading or poor cable insulation. Most of the power cables are laid in groups that run on trays. In the event of fire, cable insulation melts and cable conductors come into contact and generate sparks. The resulting flame spreads through cables and engulf other groups of cables. This leads to damage in control rooms and distribution units that causes power generation disruption and plant shutdown.To minimize the damage and system disturbance due to fire, a new system for cable installation has been developed. The system involves construction of fire stop walls using fire-resistant cavity blocks, heat-resistant wool, and fire-resistant sealant. 相似文献
Microbial leaching is one of the advantageous methods of removing heavy metals from sewage sludge, however, the microbiological aspects of this technology have not been studied. This study presents the characterization of the naturally occurring microorganisms, responsible for the metal leaching activity, in 21 different sewage sludges. The results obtained indicate that the bioleaching of metals is carried out by successive growth of less-acidophilic and acidophilic thiobacilli. Several species of less-acidophilic thiobacilli participate in the sludge acidification, but Thiobacillus thioparus is the most important species. In contrast, Thiobacillus thiooxidans seems to be the only species involved in the acidophilic group of thiobacilli. The growth kinetics of the two groups of thiobaciili was followed in five different sewage sludges. After 5 days of incubation in shake flasks, the pH of the sludge was decreased to about 2.0 and this pH decrease solubilized the toxic metals (Cd: 83–90%; Cr: 19–41%; Cu: 69–92%; Mn: 88–99%; Ni: 77–88%; Pb: 10–54%; Zn: 88–97%). The maximum specific growth rate (μmax) for the less-acidophilic thiobacilli varied between 0.079 and 0.104 h−1 and that for the acidophilic thiobacilli varied between 0.067 and 0.079 h−1. 相似文献
A conceptual model of the overall process of metal bioleaching from sewage sludge has been developed on the basis of experimental observations. Sludge pH was identified as the parameter which controls bacterial growth and thus the overall process. Quantitative relationships among the various process parameters were incorporated in the conceptual model, giving a mathematical model for the process. Bacterial growth, sulfate concentration and pH profiles simulated using the model were found to match experimental observations. The degree of solubilization of each metal was found to depend on the sludge pH and the type of the sludge and is given as a set of solubilization curves. 相似文献