Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery

This work investigates the polyanion initiated gelation process in fabricating chitosan-TPP (tripolyphosphate) nanoparticles in the size range of 100-250 nm intended to be used as carriers for the delivery of gene or protein macromolecules. It demonstrates that ionic gelation of cationic chitosan molecules offers a flexible and easily controllable process for systematically and predictably manipulating particle size and surface charge which are important properties in determining gene transfection efficacy if the nanoparticles are used as non-viral vectors for gene delivery, or as delivery carriers for protein molecules. Variations in chitosan molecular weight, chitosan concentration, chitosan to TPP weight ratio and solution pH value were examined systematically for their effects on nanoparticle size, intensity of surface charge, and tendency of particle aggregation so as to enable speedy fabrication of chitosan nanoparticles with predetermined properties. The chitosan-TPP nanoparticles exhibited a high positive surface charge across a wide pH range, and the isoelectric point (IEP) of the nanoparticles was found to be at pH 9.0. Detailed imaging analysis of the particle morphology revealed that the nanoparticles possess typical shapes of polyhedrons (e.g., pentagon and hexagon), indicating a similar crystallisation mechanism during the particle formation and growth process. This study demonstrates that systematic design and modulation of the surface charge and particle size of chitosan-TPP nanoparticles can be readily achieved with the right control of critical processing parameters, especially the chitosan to TPP weight ratio. (c) 2005 Elsevier B.V. All rights reserved.

AN IMPROVED SCANOMETRIC IMMUNOASSAY BASED ON DUAL ENLARGEMENT OF GOLD NANOPARTICLES FOR RAPID AND LOW COST PATHOGEN DETECTION

In this study, we introduce a dual enlargement of gold nanoparticles (AuNPs) for the scanometric detection of pathogenic
bacteria. After capturing the target bacteria (Campylobacter jejuni cells), the gold immunoprobes were added to create signal on a solid substrate. The signal was then amplified dually by a gold growth process and a silver enhancement resulting in stronger intensity which can easily be recognized by an unaided eye, or measured by an inexpensive flatbed scanner. The dual-enhanced nanocatalysis is herein reported for the first time, it provides valuable insight into the development of a rapid, simple and cost-effective detection format.

Influence of process parameters on fluidised hot-melt granulation and tablet pressing of pharmaceutical powders

This study investigates the influence of process parameters on the fluidised hot melt granulation of lactose and PEG 6000, and the subsequent tablet pressing of the granules. Granulation experiments were performed to assess the effect of granulation time and binder content of the feed on the resulting granule properties such as mass mean granule size, size distribution, granule fracture stress, and granule porosity. These data were correlated using the granule growth regime model. It was found that the dominant granule growth mechanisms in this melt granulation system were nucleation followed by steady growth (PEG 10–20% w/w). However, with binder contents greater than 20% w/w, the granulation mechanism moved to the “over-wet massing” regime in which discrete granule formation could not be obtained. The granules produced in the melt fluidised bed process were subsequently pressed into tablets using an industrial tablet press. The physical properties of the tablets: fracture stress, disintegration time and friability were assessed using industry standards. These analyses indicated that particle size and binder content of the initial granules influenced the mechanical properties of the tablets. It was noted that a decrease in initial granule size resulted in an increase in the fracture stress of the tablets formed.

Down-regulation of beta1,4-galactosyltransferase V is a critical part of etoposide-induced apoptotic process and could be mediated by decreasing Sp1 levels in human glioma cells.

beta1,4-Galactosyltransferase V (beta1,4GalT V; EC 2.4.1.38) is considered to be very important in glioma for expressing transformation-related highly branched N-glycans. Recently, we have characterized beta1,4GalT V as a positive growth regulator in several glioma cell lines. However, the role of beta1,4GalT V in glioma therapy has not been clearly reported. In this study, interfering with the expression of beta1,4GalT V by its antisense cDNA in SHG44 human glioma cells markedly promoted apoptosis induced by etoposide and the activation of caspases as well as processing of Bid and expression of Bax and Bak. Conversely, the ectopic expression of beta1,4GalT V attenuated the apoptotic effect of etoposide on SHG44 cells. In addition, both the beta1,4GalT V transcription and the binding of total or membrane glycoprotein with Ricinus communis agglutinin-I (RCA-I) were partially reduced in etoposide-treated SHG44 cells, correlated well with a decreased level of Sp1 that has been identified as an activator of beta1,4GalT V transcription. Collectively, our results suggest that the down-regulation of beta1,4GalT V expression plays an important role in etoposide-induced apoptosis and could be mediated by a decreasing level of Sp1 in SHG44 cells, indicating that inhibitors of beta1,4GalT V may enhance the therapeutic efficiency of etoposide for malignant glioma.

Beta1,4-galactosyltransferase V functions as a positive growth regulator in glioma.

beta1,4-galactosyltransferase V (GalT V; EC 2.4.1.38) can effectively galactosylate the GlcNAcbeta1-->6Man arm of the highly branched N-glycans that are characteristic of glioma. Previously, we have reported that the expression of GalT V is increased in the process of glioma. However, currently little is known about the role of GalT V in this process. In this study, the ectopic expression of GalT V could promote the invasion and survival of glioma cells and transformed astrocytes. Furthermore, decreasing the expression of GalT V in glioma cells promoted apoptosis, inhibited the invasion and migration and the ability of tumor formation in vivo, and reduced the activation of AKT. In addition, the activity of GalT V promoter could be induced by epidermal growth factor, dominant active Ras, ERK1, JNK1, and constitutively active AKT. Taken together, our results suggest that GalT V functioned as a novel glioma growth activator and might represent a novel target in glioma therapy.

A DFT study of the chain growth probability in Fischer-Tropsch synthesis

The chain growth probability (alpha value) is one of the most significant parameters in Fischer-Tropsch (FT) synthesis. To gain insight into the chain growth probability, we systematically studied the hydrogenation and C-C coupling reactions with different chain lengths on the stepped Co(0001) surface using density functional theory calculations. Our findings elucidate the relationship between the barriers of these elementary reactions and the chain length. Moreover, we derived a general expression of the chain growth probability and investigated the behavior of the alpha value observed experimentally. The high methane yield results from the lower chain growth rate for C-1 + C-1 coupling compared with the other coupling reactions. After C-1, the deviation of product distribution in FT synthesis from the Anderson-Schulz-Flory distribution is due to the chain length-dependent paraffin/olefin ratio. (C) 2008 Elsevier Inc. All rights reserved.

Plasma chloriding of thin-film silver - A novel process in silver-silver chloride reference electrode fabrication

Silver thin films were modified using a novel plasma modification process for the development of thin-film silver-silver chloride reference electrodes. The surface, physical, and electrochemical properties of these electrodes were investigated by atomic force microscopy, thickness and resistivity measurement techniques, as well as impedance spectroscopy and potentiometry. After plasma treatment, thin-film growth was observed and the electrodes, in general, exhibited low interface impedance and a roughened surface. Evidence of a complex surface reorganization was found. Correlating plasma conditions with film properties suggested that increasing pressure and exposure duration increased species availability, therefore governing the reaction rates, while input power appeared to influence the type of surface chemical reactions. Results also indicated that Ar/Cl-2 mixtures should be employed rather than pure chlorine plasmas. (C) 2002 The Electrochemical Society.

Nucleation and growth in fluidised hot melt granulation

Fluidised hot melt granulation (FHMG) is a novel technology for granulation process in pharmaceutical industry, which has distinct advantages over other commercial techniques. The aim of this research was to investigate granulation and the effect of process parameters that may affect FHMG process. In this work, ballotini beads were used as the model particles and Lutrol (R) F 68 Poloxamer 188 was used as meltable solid binder. In order to determine the granulation and nucleation mechanism in this co-melt FHMG system, several parameters were investigated, such as binder content, particle size of binder and particle size and hydrophobicity of ballotini. These parameters were correlated to granule size distribution, mean granule size and granule shape. Furthermore, these experimental investigations were designed so that the coalescence model could be applied to the co-melt FHMG system. The analysis indicated that the non-inertial regime extends over a relatively short time period of

The University Incubator: Insights in the Entrepreneurial Process from a Network Perspective

Research to date has identified incubator units as an effective mechanism for supporting the growth and development of small entrepreneurial firms. Advantages are gained not only from the provision of appropriate facilities and external managerial expertise on site, but also from the opportunity to develop entrepreneurial networks facilitated by the spatial proximity of incubator firms. Therefore, the research question upon which the paper is based investigates the impact of context, in other words the degree to which the networking opportunities provided by the university incubator support the small firm in its pursuit of sustainability and growth

Entrepreneurial and Business Growth and the Quest for a “Comprehensive Theory”: Tilting at Windmills?

Even though there has been sustained interest in growth for almost 50 years, relatively little is known about this phenomenon and much confusion and misunderstanding surrounds it. Based on a literature review and the articles in this special issue we make three recommendations that we believe will allow theory to advance and be applicable in practice. First, that discourse between key stakeholders is encouraged in order to achieve greater understanding. Second, that focus is placed on " growth as a process," rather than as a " change in amount." Third, that knowledge production requires inclusivity and pluralism in research perspectives and approaches. © 2010 Baylor University.

The effect of the binder size and viscosity on agglomerate growth in fluidised hot melt granulation

Fluidised hot melt granulation (FHMG) is a novel granulation technique for processing pharmaceutical powders. Several process and formulation parameters have been shown to significantly influence granulation characteristics within FHMG. In this study we have investigated the effect of the binder properties (binder particle size and binder viscosity) on agglomerate growth mechanisms within FHMG. Low-melting point co-polymers of polyoxyethylene–polyoxypropylene (Lutrol® F68 Poloxamer 188 and Lutrol® F127 Poloxamer 407) were used as meltable binders for FHMG, while standard ballotini beads were used as model fillers for this process. Standard sieve analysis was used to determine the size distribution of granules whereas we utilised fluorescence microscopy to investigate the distribution of binder within granules. This provided further insight into the growth mechanisms during FHMG. Binder particle size and viscosity were found to affect the onset time of granulation. Agglomerate growth achieved equilibrium within short time-scales and was shown to proceed by two competing processes, breakage of formed granules and re-agglomeration of fractured granules. Breakage was affected by the initial material properties (binder size and viscosity). When using binder with a small particle size (<250 µm), agglomerate growth via a distribution mechanism dominated. Increasing the binder particle size shifted the granulation mechanism such that agglomerates were formed predominantly via immersion. A critical ratio between binder diameter and filler has been calculated and this value may be useful for predicting or controlling granulation growth processes.

The use of process simulation methods in support of organisational learning in availability contracting

Traditional business models in the aerospace industry are based on a conventional supplier to customer relationship based on the design, manufacture and subsequent delivery of the physical product. Service provision, from the manufacturer's perspective, is typically limited to the supply of procedural documentation and the provision of spare parts to the end user as the product passes through the latter stages of its intended lifecycle. Challenging economic and political conditions have resulted in end users re-structuring their core business activities, particularly in the defence sector. This has resulted in the need for original equipment manufacturers (OEMs) to integrate and manage support service activities in partnership with the customer to deliver platform availability. This improves the probability of commercial sustainability for the OEM through shared operational risks while reducing the cost of platform ownership for the customer. The need for OEMs to evolve their design, manufacture and supply strategies by focusing on customer requirements has revealed a need for reconstruction of traditional internal behaviours and design methodologies. Application of organisational learning is now a well recognised principle for innovative companies to achieve long term growth and sustained technical development, and hence, greater market command. It focuses on the process by which the organisation's knowledge and value base changes, leading to improved problem solving ability and capacity for action. From the perspective of availability contracting, knowledge and the processes by which it is generated, used and retained, become primary assets within the learning organisation. This paper will introduce the application of digital methods to asset management by demonstrating how the process of learning can benefit from a digital approach, how product and process design can be integrated within a virtual framework and finally how the approach can be applied in a service context.

Eating as a neurodevelopment process for high risk newborns

Many high-risk and preterm infants have difficulty with successful feeding and subsequent optimal growth during their stay in the neonatal intensive care unit as well as in the months after discharge. Environmental, procedural, and medical issues necessary for treatment of the hospitalized infant present challenges for the development of successful eating skills. Emerging data describe eating as a predictable neurodevelopmental process that depends on the infant’s organization of physiologic processes, motor tone and movement, level of arousal, and ability to simultaneously regulate these processes.