Mesoporous matrices for the delivery of the broad spectrum bacteriocin, Nisin A

peer-reviewedMesoporous matrices of different pore size and chemical composition were explored as potential delivery matrices for the broad spectrum bacteriocin, nisin A. The adsorption of nisin A onto two mesoporous silicates (MPS - SBA-15, MCM-41) and two periodic mesoporous organosilanes (PMO - MSE, PMO-PA) was examined. It was found that hydrophobic interactions dominated in the adsorption of this peptide to the matrices, lending the highest adsorption to MCM-41 with a small pore size of 2.8 nm. The hydrophobic ethylene-bridged MSE (6 nm pore) improved the loading and protection of nisin A from degradation by a non-specific protease pepsin, over un-functionalised SBA-15 which had a slightly larger pore size and less hydrophobic moieties. Nisin A did not adsorb onto an amine-functionalised PMO. Upon suspension in modified fasted state simulated gastric fluid (pH 1.6), the highest release of nisin A was observed from MCM-41, with a lower release from SBA-15 and MSE, with release following Higuchi release kinetics. No release was detected into modified fasted state simulated intestinal fluid (pH 6.5) but despite this, the suspended matrices loaded with nisin A remained active against Staphylococcus aureus

Complement C3 activation is required for antiphospholipid antibody-induced fetal loss

The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis, and thrombocytopenia occurring in the presence of antiphospholipid (aPL) antibodies. The pathogenesis of fetal loss and tissue injury in APS is incompletely understood, but is thought to involve platelet and endothelial cell activation as well as procoagulant effects of aPL antibodies acting directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation in the placenta leads to fetal death in utero. We hypothesized that aPL antibodies activate complement in the placenta, generating split products that mediate placental injury and lead to fetal loss and growth retardation. To test this hypothesis, we used a murine model of APS in which pregnant mice are injected with human IgG containing aPL antibodies. We found that inhibition of the complement cascade in vivo, using the C3 convertase inhibitor complement receptor 1–related gene/protein y (Crry)-Ig, blocks fetal loss and growth retardation. Furthermore, mice deficient in complement C3 were resistant to fetal injury induced by aPL antibodies. While antigenic epitopes recognized by aPL antibodies are important in the pathogenesis of APS, our data show that in vivo complement activation is required for aPL antibody-induced fetal loss and growth retardation. Key words: complement • anticardiolipin antibodies • pregnancy • thrombosis • lupu

Inclusion of fenofibrate in a series of mesoporous silicas using microwave irradiation

A selection of porous silicas were combined with a model drug using a recently developed, controlled microwave heating process to determine if the application of microwave irradiation could enhance subsequent drug release. Five mesoporous silica types were investigated (core shell, core shell rehydrox, SBA-15, silica gel, SYLOID®) and, for comparison, one non-porous silica (stober). These were formulated using a tailored microwave heating method at drug:excipient ratios of 1:1, 1:3 and 1:5. In addition, all experiments were performed both in the presence and absence of water, used as a fluidising media to aid interaction between drug and support, and compared with results obtained using more traditional heating methods. All formulations were then characterized using differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transformation infrared spectroscopy (FT-IR). Pharmaceutical performance was investigated using in vitro drug release studies. A significant enhancement in the release profile of fenofibrate was observed for formulations prepared using microwave heating in the absence of water for five of the six silica based formulations. Of all the formulations analysed, the greatest extent of drug release within the experimental 30 minutes was the 1:5 core shell rehydrox achieveing a total of 86.6% ±2.8%. The non porous (stober) particles did not exhibit an increased release of the drug under any experimental conditions studied. This anomaly is thought to be a result of the comparatively small surface area of the silica particles thus preventing the adsorption of drug molecules