Boron nitride nanotubes : a novel vector for targeted magnetic drug delivery

Whereas several biomedical applications of carbon nanotubes have been proposed, the use of boron nitride nanotubes (BNNTs) in this field has been largely unexplored despite their unique and potentially useful properties. Our group has recently initiated an experimental program aimed at the exploration of the interactions between BNNTs and living cells. In the present paper, we report on the magnetic properties of BNNTs containing Fe catalysts which confirm the feasibility for their use as nanovectors for targeted drug delivery. The magnetisation curves of BNNTs characterised by the present study are typical of superparamagnetic materials with important parameters, including magnetic permeability and magnetic momentum, derived by employing Langevin theory. In-vitro tests have demonstrated the feasibility for influencing the uptake of BNNTs by living cells by exposure to an external magnetic source. A finite element method analysis devised to predict this effect produced predictive data with close agreement with the experimental observations.

Recent advances in nanoneurology for drug delivery to the brain

The drug development for neurodegenerative disorders are the major challenge to the science in 21st century. Many FDA approved drugs currently available in the market have limitations in crossing the blood brain barrier (BBB) owing to its complicated vasculature posed by the presence of specialized cells. Nanotechnology is an emerging interdisciplinary area, which have many applications including drug delivery. Nanocarrier drug delivery involves targeting drugs enclosed in a particular polymer and/or amphiphilic lipids. Controlled release, nanoplatform availability for combinatorial therapy and tissue specific targeting by using advanced technologies such as molecular Trojan horse (MTH) technology are the promises of nanotechnology. Different problems are associated with drug delivery
across the BBB. Some are mostly related to the structure of brain microvasculature system while the others are related to the nanomaterial
structure. Different strategies, such as using polymeric/solid lipid nanoparticles and surface modification of nanomaterial with surfactants
like polysorbates have been conducted to solve these limitations. Also, nanodrug formulations with double coatings have been designed for oral delivery of drugs to overcome reticulo-endothelial system and to improve their BBB permeability. It seems that the best choice of strategy and material could be achieved with regard to the physical and chemical structure of the drugs. The present review discusses the potential applications of nanotechnology for drug delivery across the BBB.

Promises of nanotechnology for drug delivery to brain in neurodegenerative diseases

Brain is a delicate organ, isolated from general circulation and characterized by the presence of relatively impermeable endothelial cells with tight junctions, enzymatic activity and the presence of active efflux transporter mechanisms. These formidable obstacles often block drug delivery to the brain across the blood-brain barrier (BBB). Although several promising molecules have the potential in the in vitro settings but lack of in vivo response is probably because the molecule cannot reach the brain in a sufficient concentration. Drug delivery across the BBB is a major limitation in the treatment of central nervous system (CNS) disorders and CNS infections. This review deals with the role of nanobiotechnology in CNS drug delivery, in which three categories of carbon nanotubes, nanowires and nanoparticles (NPs) are explained. The small size of the NPs makes them an ideal choice to penetrate the BBB. Several mechanisms are involved in this process and various strategies are used. There are some concerns about the safety of NP entry in the brain that need to be resolved before human use. Although there is no approved nanotechnology-based CNS drug available the future for such neuro-nanobiotechnology based delivery system developments is promising.

Design and construction of a micropump for drug delivery applications

This paper presents design, construction, and evaluation of a micropump for drug delivery applications. The proposed micropump consists of three components: fluidics, electronics, and software. The fluidics component includes a silicone elastic diaphragm, a microservo, housing and two check valves. The diaphragm is modeled and simulated to establish its geometrical specifications. The housing is built using a rapid prototype machine. The electronics component consists of a microcontroller, a microswitch array, a simple display and a power unit. The software component is written in C and receives inputs from user, controls the microservo speed and displays the programmed speed. A number of experiments are conducted to evaluate the performance and capabilities of the micropump. The experiments focus on measurement of flow rate, dosage and duration of operation. A discussion of the performance and capabilities of the developed micropump is also given.

Comparison of two modes of delivery of first aid training

This study found that first aid competencies of participants assessed three months after standard two-day, classroom-based first aid courses, were similar to those assessed three months after flexible learning courses in which participants undertook home study using a text and on-line theory questionnaire, followed by a day of classroom training.

Comparison of two modes of delivery of first aid training including basic life support

Aims: Flexible-learning first aid courses are increasingly common due to reduced classroom contact time. This study compared retention of first aid knowledge and basic life support (BLS) skills three months after a two-day, classroom-based first aid course (STD) to one utilizing on-line theory learning at home followed by one day of classroom training (FLEX).
Methods: In this prospective randomized controlled trial, 256 participants with internet access and no first aid related training for at least five years were randomly allocated to a STD or FLEX course. Assessment was conducted immediately after training and again three months later. Each participant was allocated a theory and a BLS score, which were summed and averaged to create an equally-weighted ‘combined score’
of first aid knowledge and skills.
Results: There was no significant difference in theory scores between the STD and FLEX groups immediately after training and after three months. STD participants had significantly higher BLS scores immediately after training (p = 0.001) and three months later (p = 0.046). Males had significantly higher BLS scores after training (p < 0.001), but not three months later (p = 0.02). Participants older than 46 years had significantly lower BLS scores than younger participants (p < 0.001). There was no significant difference in combined scores between the STD and FLEX groups or between genders, education or age groups either immediately after training or three months later.
Conclusion: After replacing one day of classroom-based training with on-line theory training, there was no significant difference in the first aid competencies of the study population, as measured by an equallyweighted
combined score of basic life support and first aid theory.

Performance analysis of cyber security awareness delivery methods

In order to decrease information security threats caused by human-related vulnerabilities, an increased concentration on information security awareness and training is necessary. There are numerous information security awareness training delivery methods. The purpose of this study was to determine what delivery method is most successful in providing security awareness training. We conducted security awareness training using various delivery methods such as text based, game based and a short video presentation with the aim of determining user preference delivery methods. Our study suggests that a combined delvery methods are better than individual secrity awareness delivery method.

Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1)

Multidrug ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1) and multidrug resistance protein 1 (MRP1/ABCC1) play an important role in the extrusion of drugs from the cell and their overexpression can be a cause of failure of anticancer and antimicrobial chemotherapy. Recently, the mouse P-gp/Abcb1a structure has been determined and this has significantly enhanced our understanding of the structure-activity relationship (SAR) of mammalian ABC transporters. This paper highlights our current knowledge on the structural and functional properties and the SAR of human MRP1/ABCC1. Although the crystal structure of MRP1/ABCC1 has yet to be resolved, the current topological model of MRP1/ABCC1 contains two transmembrane domains (TMD1 and TMD2) each followed by a nucleotide binding domain (NBD) plus a third NH2-terminal TMD0. MRP1/ABCC1 is expressed in the liver, kidney, intestine, brain and other tissues. MRP1/ABCC1 transports a structurally diverse array of important endogenous substances (e.g. leukotrienes and estrogen conjugates) and xenobiotics and their metabolites, including various conjugates, anticancer drugs, heavy metals, organic anions and lipids. Cells that highly express MRP1/ABCC1 confer resistance to a variety of natural product anticancer drugs such as vinca alkaloids (e.g. vincristine), anthracyclines (e.g. etoposide) and epipodophyllotoxins (e.g. doxorubicin and mitoxantrone). MRP1/ABCC1 is associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents. However, most compounds that efficiently reverse P-gp/ABCB1-mediated multidrug resistance have only low affinity for MRP1/ABCC1 and there are only a few effective and relatively specific MRP1/ABCC1 inhibitors available. A number of site-directed mutagenesis studies, biophysical and photolabeling studies, SAR and QSAR, molecular docking and homology modeling studies have documented the role of multiple residues in determining the substrate specificity and inhibitor selectivity of MRP1/ABCC1. Most of these residues are located in the TMs of TMD1 and TMD2, in particular TMs 4, 6, 7, 8, 10, 11, 14, 16, and 17, or in close proximity to the membrane/cytosol interface of MRP1/ABCC1. The exact transporting mechanism of MRP1/ABCC1 is unclear. MRP1/ABCC1 and other multidrug transporters are front-line mediators of drug resistance in cancers and represent important therapeutic targets in future chemotherapy. The crystal structure of human MRP1/ABCC1 is expected to be resolved in the near future and this will provide an insight into the SAR of MRP1/ABCC1 and allow for rational design of anticancer drugs and potent and selective MRP1/ABCC1 inhibitors.

A novel nanoplatform for oral delivery of anti-cancer biomacromolecules

Oral administration of bio–macromolecules is an uphill task and the challenges from varying pH and enzymatic activity are difficult to overcome. In this regard, nanotechnology promises the new hope and offers advantages such as controlled release, target specific delivery, combinatorial therapy and many more. In this study, we demonstrate the formulation of a novel alginate enclosed, chitosan coated ceramic, anti cancer nano carrier (ACSC NC). These NC were loaded with multi functional anti cancer bovine lactoferrin (Lf), a natural milk based protein, for improvement of intestinal absorption, in order to develop a novel platform to carry anti cancer protein and/or peptides for oral therapy. Here we demonstrate the size, morphology, internalisation and release profiles of the nanoparticles (NC) under varying pH as perceived in human digestive system. We further determine the uptake of these particles by colon cancer cell lines by measuring the endocytosis and transcytosis of the NC. These NC can be used for future targeted protein/peptide or nucleic acid based drug delivery to treat difficult diseases including cancer.

Formulation optimization for high drug loading colonic drug delivery carrier

High drug loading (DL) carrier is an effective way to cure the cancerous cells. High drug loading is also one of the key issues in the drug delivery research, especially the colonic drug delivery system by oral administration. The times of drug intake could be remarkably reduced if high drug loading carriers are administered. At the same time, the related formulation materials could be effectively utilized. One major obstacle with the preparation of this system is the difficulty to encapsulate the hydrophilic drug into hydrophobic encapsulation polymer. A design of high drug loading delivery system with biodegradable, biocompatible materials and optimization of the fabrication process is a potential solution to solve the problem. So in this research, 5-Fluorouracil (5-FU) loaded Poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared by double emulsion and solvent evaporation method. Several fabrication parameters including theoretical drug loading, volume ratio of outer water phase to the first emulsion, pH value of outer aqueous phase and emulsifier PVA concentration were optimized to get a high drug loading nanoparticles. The result shows that with the increase of theoretical drug loading, the actual drug loading increased gradually. When adjusted the pH value of outer aqueous phase to the isoelectric point (8.02) of 5-Fluorouracil, the drug loading exhibited a higher one compared to other pH value solution. Relative higher volume ratio of outer water phase to the first emulsion was also beneficial for the enhancement of drug loading. But the nanoparticles size increased simultaneously due to the lower shearing force. When increased the PVA concentration, the drug loading showed an increase first and following a drop.

Challenges to infrastructure delivery during the economic downturn : a qualitative analysis

Infrastructure plays a key role in creating and maintaining sustainable economic growth and a prosperous community. Infrastructure projects generally require a large amount of capital investment, which motivates involvement from the private sector in the delivery process. The Global Financial Crisis placed enormous pressure on both the public and private sectors, as the ability to borrow money for an extended tenor was greatly reduced. This study adopts a qualitative approach to analyse the challenges facing the delivery of infrastructure projects in an Australian context by considering the impacts of the Global Financial Crisis. It is found that the availability of resources and finance are perceived as the biggest challenges, with resources being more of a concern than finance to interviewees. In addition to these findings, ways in which the private sector can be better involved in the infrastructure delivery is discussed.