Fabrication and characterization of gold coated hollow silicon microneedle array for drug delivery

In this paper, we present the fabrication and characterization of Ti and Au coated hollow silicon microneedles for transdermal drug delivery applications. The hollow silicon microneedles are fabricated using isotropic etching followed by anisotropic etching to obtain a tapered tip. Silicon microneedle of 300 mu m in height, with 130 mu m outer diameter and 110 mu m inner diameter at the tip followed by 80 mu m inner diameter and 160 mu m outer diameter at the base have been fabricated. In order to improve the biocompatibility of microneedles, the fabricated microneedles were coated with Ti (500 nm) by sputtering technique followed by gold coating using electroplating. A breaking force of 225 N was obtained for the fabricated microneedles, which is 10 times higher than the skin resistive force. Hence, fabricated microneedles can easily be inserted inside the skin without breakage. The fluid flow through the microneedles was studied for different inlet pressures. A minimum inlet pressure of 0.66 kPa was required to achieve a flow rate of 50 mu l in 2 s with de-ionized water as a fluid medium. (C) 2014 Elsevier B.V. All rights reserved.

Efficacious redox-responsive gene delivery in serum by ferrocenylated monomeric and dimeric cationic cholesterols

Herein, we present the design and synthesis of new redox-active monomeric and dimeric (gemini) cationic lipids based on ferrocenylated cholesterol derivatives for gene delivery. The cationic cholesterols are shown to be transfection efficient after being formulated with the neutral helper lipid DOPE in the presence of serum (FBS). The redox activity of the resulting co-liposomes and their lipoplexes could be regulated using the alkanyl ferrocene moiety attached to the ammonium head groups of the cationic cholesterols. Atomic force microscopy (AFM), dynamic light scattering (DLS) and zeta potential measurements were performed to characterize the co-liposomal aggregates and their complexes with pDNA. The transfection efficiency of lipoplexes could be tuned by changing the oxidation state of the ferrocene moiety. The gene transfection capability was assayed in terms of green fluorescence protein (GFP) expression using pEGFP-C3 plasmid DNA in three cell lines of different origins, namely Caco-2, HEK293T and HeLa, in the presence of serum. The vesicles possessing ferrocene in the reduced state induced an efficient transfection, even better than a commercial reagent Lipofectamine 2000 (Lipo 2000) as evidenced by flow cytometry and fluorescence microscopy. All the co-liposomes containing the oxidized ferrocene displayed diminished levels of gene expression. Gene transfection events from the oxidized co-liposomes were further potentiated by introducing ascorbic acid (AA) as a reducing agent during lipoplex incubation with cells, leading to the resumption of transfection activity. Assessment of transfection capability of both reduced and oxidized co-liposomes was also undertaken following cellular internalization of labelled pDNA using confocal microscopy and flow cytometry. Overall, we demonstrate here controlled gene transfection activities using redox-driven, transfection efficient cationic monomeric and dimeric cholesterol lipids. Such systems could be used in gene delivery applications where transfection needs to be performed spatially or temporally.

Development of cup shaped microneedle array for transdermal drug delivery

Microneedle technology is one of the attractive methods in transdermal drug delivery. However, the clinical applications of this method are limited owing to: complexity in the preparation of multiple coating solutions, drug leakage while inserting the microneedles into the skin and the outer walls of the solid microneedle can hold limited quantity of drug. Here, the authors present the fabrication of an array of rectangular cup shaped silicon microneedles, which provide for reduced drug leakage resulting in improvement of efficiency of drug delivery and possibility of introducing multiple drugs. The fabricated solid microneedles with rectangular cup shaped tip have a total height of 200 mu m. These cup shaped tips have dimensions: 60 x 60 mu m (length x breadth) with a depth of 60 mu m. The cups are filled with drug using a novel in-house built drop coating system. Successful drug dissolution was observed when the coated microneedle was used on mice. Also, using the above method, it is possible to fill the cups selectively with different drugs, which enables simultaneous multiple drug delivery. (C) 2015 American Vacuum Society.

Delivery of small nucleic acids by conjugation to carbohydrates and lipids as novel research and therapeutic tools

399 p. : il., graf.

Delivery of Targeted Nanoparticles Across the Blood-Brain Barrier Using a Detachable Targeting Ligand

Chronic diseases of the central nervous system are poorly treated due to the inability of most therapeutics to cross the blood-brain barrier. The blood-brain barrier is an anatomical and physiological barrier that severely restricts solute influx, including most drugs, from the blood to the brain. One promising method to overcome this obstacle is to use endogenous solute influx systems at the blood-brain barrier to transport drugs. Therapeutics designed to enter the brain through transcytosis by binding the transferrin receptor, however, are restricted within endothelial cells. The focus of this work was to develop a method to increase uptake of transferrin-containing nanoparticles into the brain by overcoming these restrictive processes.

To accomplish this goal, nanoparticles were prepared with surface transferrin molecules bound through various liable chemical bonds. These nanoparticles were designed to shed the targeting molecule during transcytosis to allow increased accumulation of nanoparticles within the brain.

Transferrin was added to the surface of nanoparticles through either redox or pH sensitive chemistry. First, nanoparticles with transferrin bound through disulfide bonds were prepared. These nanoparticles showed decreased avidity for the transferrin receptor after exposure to reducing agents and increased ability to enter the brain in vivo compared to those lacking the disulfide link.

Next, transferrin was attached through a chemical bond that cleaves at mildly acidic pH. Nanoparticles containing a cleavable link between transferrin and gold nanoparticle cores were found to both cross an in vitro model of the blood-brain barrier and accumulate within the brain in significantly higher numbers than similar nanoparticles lacking the cleavable bond. Also, this increased accumulation was not seen when using this same strategy with an antibody to transferrin receptor, indicating that behavior of nanoparticles at the blood-brain barrier varies depending on what type of targeting ligand is used.

Finally, polymeric nanoparticles loaded with dopamine and utilizing a superior acid-cleavable targeting chemistry were investigated as a potential treatment for Parkinson’s disease. These nanoparticles were capable of increasing dopamine quantities in the brains of healthy mice, highlighting the therapeutic potential of this design. Overall, this work describes a novel method to increase targeted nanoparticle accumulation in the brain.

Specifying a hydraulic regenerative braking system for an articulated urban delivery vehicle

Previous research has shown that hydraulic systems offer potentially the lightest and smallest regenerative braking technology for heavy goods vehicles. This paper takes the most practical embodiment of a hydraulic system for an articulated urban delivery vehicle and investigates the best specification for the various components, based on a simulated stop-start cycle. The potential energy saving is quantified. © 2011 IEEE.

Product Service Systems and supply network relationships: An exploratory case study

Purpose - In recent years there has been increasing interest in Product Service Systems (PSSs) as a business model for selling integrated product and service offerings. To date, there has been extensive research into the benefits of PSS to manufacturers and their customers, but there has been limited research into the effect of PSS on the upstream supply chain. This paper seeks to address this gap in the research. Design/methodology/approach - The research uses case-based research which is appropriate for exploratory research of this type. In-depth interviews were conducted with key personnel in a focal firm and two members of its supply chain, and the results were analysed to identify emergent themes.b Findings - The research has identified differences in supplier behaviour dependent on their role in PSS delivery and their relationship with the PSS provider. In particular, it suggests that for a successful partnership it is important to align the objectives between PSS provider and suppliers. Originality/value - This research provides a detailed investigation into a PSS supply chain and highlights the complexity of roles and relationships among the organizations within it. It will be of value to other PSS researchers and organizations transitioning to the delivery of PSS. © Emerald Group Publishing Limited.

Building more sustainable solutions in production-consumption systems: the case of food for people with reduced access

In new product development, the ability to integrate different dimensions of sustainability at a value chain level is still a complex, problematic goal. As product-service approaches are increasingly enabling the introduction of more sustainable paths, this paper describes the authors' experience thus far when building insights into conditions for the implementation of integrated solutions in a process of co-development and testing in real life conditions, which are driven by a social need focusing on food for people with reduced access. Throughout this process, which brought together producers, consumers and other stakeholders to design and test industrialised, sustainable solutions, empirical evidence demonstrates feasibility and usefulness of the approach and insight into the conditions for implementing interactive, comprehensive multi-stakeholder processes in real life situations. In addition, results show that the delivery of innovative solutions enabled to offer social added value, economic profits and environmental improvements under specific experimental conditions. © 2006 Elsevier Ltd. All rights reserved.

Voltage sensing buck converter-based technique for maximum photovoltaic solar energy delivery

A voltage sensing buck converter-based technique for maximum solar power delivery to a load is presented. While retaining the features and advantages of the incremental conductance algorithm, this technique is more desirable because of single sensor use. The technique operates by maximising power at the buck converter output instead of the input.

automated test case generation for the stress testing of multimedia systems

With the advancement in network bandwidth and computing power, multimedia systems have become a popular means for information delivery. However, general principles of system testing cannot be directly applied to testing of multimedia systems on account of their stringent temporal and synchronization requirements. In particular, few studies have been made on the stress testing of multimedia systems with respect to their temporal requirements under resource saturation. Stress testing is important because erroneous behavior is most likely to occur under resource saturation. This paper presents an automatable method of test case generation for the stress testing of multimedia systems. It adapts constraint solving techniques to generate test cases that lead to potential resource saturation in a multimedia system. Coverage of the test cases is defined upon the reachability graph of a multimedia system. The proposed stress testing technique is supported by tools and has been successfully applied to a real-life commercial multimedia system. Although our technique focuses on the stress testing of multimedia systems, the underlying issues and concepts are applicable to other types of real-time systems.

Fabrication, characterization of spherical CaWO4:Ln@MCM-41(Ln=Eu3+, Dy3+, Sm3+, Er3+) composites and their applications as drug release systems

Spherical MCM-41 particles with a diameter of about 150 nm have been successfully coated with CaWO4:Ln (Ln = Eu3+, Dy3+, Sm3+, Er3+) phosphor layers through a simple Pechini sol-gel process. The obtained CaWO4:Ln@MCM-41 composites, which kept the mesoporous structure of MCM-41 and the luminescent properties of phosphors, were investigated as a drug delivery system using aspirin (ASPL) as a model drug.

MCM-41 functionalized with YVO4 : Eu3+: a novel drug delivery system

Luminescence functionalization of ordered mesoporous MCM-41 silica was realized by depositing a YVO4:Eu3+ phosphor layer on its surface via the Pechini sol-gel process. This material, which combines the mesoporous structure of MCM-41 and the strong red luminescence property of YVO4: Eu3+, has been studied as a host carrier for drug delivery/release systems. The structure, morphology, texture and optical properties of the materials were well characterized by x-ray diffraction ( XRD), Fourier infrared spectroscopy ( FT-IR), transmission electron microscopy ( TEM), N-2 adsorption and photoluminescence ( PL) spectra. The results indicated that the specific surface area and pore volume of MCM-41, which were directly correlated to the drug-loading amount and ibuprofen ( IBU) release rate, decreased in sequence after deposition of YVO4:Eu3+ and loading of IBU as expected. The IBU-loaded YVO4:Eu3+@ MCM-41 system still showed red luminescence under UV irradiation ( 365 nm) and a controlled release property for IBU. In addition, the emission intensity of Eu3+ increases with an increase in the cumulative released amount of IBU, making the extent of drug release easily identified, tracked and monitored by the change of luminescence, which demonstrates its potential application in drug delivery/release systems.

Enantiomeric PLA-PEG block copolymers and their stereocomplex micelles used as rifampin delivery

A novelty approach to self-assembling stereocomplex micelles by enantiomeric PLA-PEG block copolymers as a drug delivery carrier was described. The particles were encapsulated by enantiomeric PLA-PEG stereocomplex to form nanoscale micelles different from the microspheres or the single micelles by PLLA or PDLA in the reported literatures. First, the block copolymers of enantiomeric poly(L-lactide)-poly(ethylene-glycol) (PLLA-PEG) and poly(D-lactide)-poly(ethylene-glycol) (PDLA-PEG) were synthesized by the ring-opening polymerization of L-lactide and D-lactide in the presence of monomethoxy PEG, respectively. Second, the stereocomplex block copolymer micelles were obtained by the self-assembly of the equimolar mixtures of enantiomeric PLA-PEG copolymers in water. These micelles possessed partially the crystallized hydrophobic cores with the critical micelle concentrations (cmc) in the range of 0.8-4.8 mg/l and the mean hydrodynamic diameters ranging from 40 to 120 nm. The micelle sizes and cmc values obviously depended on the hydrophobic block PLA content in the copolymer.Compared with the single PLLA-PEG or PDLA PEG micelles, the cmc values of the stereocomplex micelles became lower and the sizes of the stereocomplex micelles formed smaller. And lastly, the stereocomplex micelles encapsulated with rifampin were tested for the controlled release application.

dPAM: A Distributed Prefetching Protocol for Scalable Asynchronous Multicast in P2P Systems

We leverage the buffering capabilities of end-systems to achieve scalable, asynchronous delivery of streams in a peer-to-peer environment. Unlike existing cache-and-relay schemes, we propose a distributed prefetching protocol where peers prefetch and store portions of the streaming media ahead of their playout time, thus not only turning themselves to possible sources for other peers but their prefetched data can allow them to overcome the departure of their source-peer. This stands in sharp contrast to existing cache-and-relay schemes where the departure of the source-peer forces its peer children to go the original server, thus disrupting their service and increasing server and network load. Through mathematical analysis and simulations, we show the effectiveness of maintaining such asynchronous multicasts from several source-peers to other children peers, and the efficacy of prefetching in the face of peer departures. We confirm the scalability of our dPAM protocol as it is shown to significantly reduce server load.