Self-assembled dextrin nanogel as protein carrier : controlled release and biological activity of IL-10

Interleukin-10 (IL-10) is an anti-inflammatory cytokine, which active form is a non-covalent homodimer. Given the potential of IL-10 for application in various medical conditions, it is essential to develop systems for its effective delivery. In previous work, it has been shown that a dextrin nanogel effectively incorporated and stabilized rIL10, enabling its release over time. In this work, the delivery system based on dextrin nanogels was further analyzed. The biocompatibility of the nanogel was comprehensively analyzed, through cytotoxicity (lactate dehydrogenase release, MTS, Live and Dead) and genotoxicity (comet) assays. The release profile of rIL-10 and its biological activity were evaluated in vivo, using C57BL/6 mice. Although able to maintain a stable concentration of IL-10 for at least 4 hours in mice serum, the amount of protein released was rather low. Despite this, the amount of rIL-10 released from the complex was biologically active inhibiting TNF-α production, in vivo, by LPSchallenged mice. In spite of the significant stabilization achieved using the nanogel, rIL-10 still denatures rather quickly. An additional effort is thus necessary to develop an effective delivery system for this cytokine, able to release active protein over longer periods of time. Nevertheless, the good biocompatibility, the protein stabilization effect and the ability to perform as a carrier with controlled release suggest that self-assembled dextrin nanogels may be useful protein delivery systems.Contract grant sponsor: Fundacao para a Ciencia e Tecnologia (FCT), PortugalContract grant number: SFRH/BD/27359/2006Contract grant sponsor: FCTContract grant number: PTDC/BIO/67160/2006; SUDOE-FEDERIMMUNONETSOE1/P1/E01

Rapid analytical techniques for ondansetron

Available from British Library Document Supply Centre-DSC:DXN025015 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Implementing Intranet Support for BPR in a Small Manufacturing Company

This paper describes the practical manner in which an intranet was applied to a small manufacturing company to support its BPR programme. The company is involved in the design and manufacture of speciality knitting machines. Its market share and turnover have been improving rapidly over recent years and as a consequence the increase in workload has resulted in an increasing focus on short-term operational problems. It was recognised that if the business were to retain a competitive edge in its markets, organisational and strategic issues would have to be considered further. The company therefore embarked on a long-term development programme to define key business and manufacturing strategies, their associated business processes and the supporting organisational and information technology systems. A BPA (Business Process Analysis) exercise and strategic re-alignment has been under¬taken and a change methodology defined. A BPR (Business Process Re-engineering) implementation is currently in progress, driven by the above methodology and underpinned by the implementation of a pilot company intranet

Stability of freeze-dried pH-responsive dextrin nanogels containing doxorubicin

© 2016 The Authors. Induction of non-specific toxicities by doxorubicin (DOX) has restricted conventional DOX-based chemotherapy. pH-responsive dextrin nanogels (DNGs) have been fabricated in order to incorporate and deliver DOX to specific (targeted) sites. However, adequate stability studies of DOX-loaded DNGs are required for selection of storage conditions. The aim of this study was therefore to evaluate the accelerated (25?°C/60% RH) and long-term (5?°C) stability of DNGs prepared with formaldehyde (FDNGs) and glyoxal (GDNGs) as cross-linker by determining the change in their physicochemical properties. The mean diameter decreased with time during long-term storage. The drug content between freshly prepared (initial day) and after storage at 5?°C for 180 days of DOX-loaded FDNGs and DOX-loaded GDNGs was not significantly different (p?>?0.05), but decreased after storage under the accelerated condition. The release of DOX from all DNGs was pH-dependent. However, DNGs kept under the accelerated condition showed higher amount of DOX release than those stored at 5?°C and the freshly prepared ones. The results indicate that the stability of DNGs could be improved by their storage at 5?°C

Dextrin–Colistin Conjugates as a Model Bioresponsive Treatment for Multidrug Resistant Bacterial Infections

Polymer therapeutics offer potential benefits in the treatment of multidrug resistant (MDR) infections; affording targeted delivery of biologically active agents to the site of inflammation, potential decreases in systemic toxicity, and the retention of antimicrobial activity at the target site. As a prototype model, these studies developed and characterized a library of dextrin–colistin conjugates (dextrin molecular weight: 7500–48 000 g/mol) as a means of targeting the delivery of colistin. Optimum colistin release kinetics (following dextrin degradation by physiological concentrations of amylase (100 IU/L)) were observed in conjugates containing low molecular weight (∼7500 g/mol) dextrin with ∼1 mol % succinoylation (∼80% drug release within 48 h, compared to ∼33% from sodium colistin methanesulfonate (CMS, Colomycin)). These conjugates exhibited comparable antimicrobial activity to CMS in conventional MIC assays against a range of Gram-negative pathogens, but with significantly reduced in vitro toxicity toward kidney (IC50 = CMS, 15.4 μg/mL; dextrin–colistin, 63.9 μg/mL) and macrophage (IC50 = CMS, 111.3 μg/mL; dextrin–colistin, 303.9 μg/mL) cells. In vivo dose-escalation studies in rats demonstrated improved pharmacokinetics of the conjugates, with prolonged plasma levels of colistin (t1/2 135–1271 min vs 53 min) and decreased toxicity, compared to colistin sulfate. These studies highlight the potential utility of “nanoantibiotic” polymer therapeutics to aid the safe, effective, and targeted delivery of colistin in the management of MDR infections