Current Nanoscience - Volume 5, Issue 4, 2009

Nanotechnology is proving to play a major role in the future of biomedical applications such as drug delivery, gene therapy and cell imaging/tracking, in particular the use of nanoparticles is regularly highlighted. However with regards to nanoparticles, direct intracellular and intranuclear delivery has, until recently, been difficult to achieve due to the impermeable nature of the plasma and nuclear membranes. The advent of cell penetrating peptides being employed as delivery vectors has opened up many avenues with respect to targeted delivery systems. In this paper, quantum dots were synthesised and functionalised with the HIV-1 tat peptide, and uptake into human bone marrow derived cell populations was assessed. Results demonstrated an increase in uptake for tat modified quantum dots, possibly via a different mechanism to non-modified dots.

The neglected diseases have not received any especial public and private attention in the last years, as for example, some parasitic diseases. Considerable amounts of private and public money are needed to apply nanobiotechnology for the treatment of neglected diseases. This review focuses on malaria, leishmaniasis, schistosomiasis, trypanosomiasis, tuberculosis, leprosy and filiarasis, and onchocerciasis where liposomes, polymeric nanoparticles or nanostructured lipid carriers have been applied. These nanocarrier systems have shown promissing results in the treatment of many neglected diseases with diminished toxicity and increased efficacy as well as a prolonged release with a reduced number of dosages. Despite these promising results, few nanocarriers have been used in clinical tests. As far as we know, these references are a minority compared to the number of studies of drug delivery systems that have been published in the last years. Therefore, the challenge for the researchers in this area is to generate interest amongst the governments and industries for the treatment of neglected diseases.

The objective of the study was to evaluate the efficacy of insulin loaded polymerosomes in diabetic rat model. To achieve the purpose, amphiphilic triblock co-polymers of the class poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone), CEC were synthesized by ring-opening polymerization and characterized. Polymerosomes were prepared by double emulsion method in the size range of 75-130 nm at 25 °C as measured by differential light scattering technique. Insulin was loaded in situ during nanoparticle preparation. The release of insulin was observed to be critically dependent on the caprolactone/ethylene glycol ratio and particle size. The pharmacological activity ranged from 22-36 h for various polymerosomes formulations in comparison to poly(caprolactone), PCL nanoparticles which reached the basal level after 4 h of administration. The polymerosomes were therefore seen to enhance the insulin activity as well as its stability in physiological fluid for a prolonged duration.

Nanosuspensions have attracted much interest of many scientists as a new approach to deliver poorly soluble drugs because of their process flexibility and special advantages such as improved oral bioavailability, high drug loading, targeting capabilities and so on. Recently, the manufacture processes of nanosuspensions have developed quickly, and some new methods have emerged, for example, controlled precipitation, emulsion method, microemulsion method and melt-emulsion method. Additionally, the post-process of nanosuspension has also gained great progresses to expand the utility of nanosuspensions, including solidification technique and surface modification technique. Moreover, the study on targeting delivery by nanosuspension following intravenous administration has become a hot topic of many researches. In the article, we will highlight new developments in the production of nanosuspensions and summarize the application of nanosuspensions via a variety of administration routes. In the end, we will overview the research and development prospectives of nanosuspensions.

The aim of present investigation was to develop novel oil-in-water (o/w) nanoemulsion based formulation containing atorvastatin for enhancing its oral bioavailability. Solubility of atorvastatin in oil, surfactant and co-surfactant was determined to select the formulation ingredients. Pseudo ternary phase diagrams were constructed by aqueous titration technique and various nanoemulsion formulations were prepared. Formulations taken from o/w nanoemulsion region were subjected to thermodynamic stability and dispersibility tests in order to eliminate metastable formulations in minimum possible time. In vitro drug release was performed by dialysis bag method and compared with the release of drug from suspension and conventional marketed tablet. The optimized formulation showed higher drug release (99.34%), lower droplet size (42.8 ± 0.42 nm), lower polydispersity (0.237 ± 0.012), less viscosity (27.51 ± 1.01 cP) and infinite dilution capability. A pharmacokinetic study was performed after oral administration of atorvastatin at 6 mg/kg in wistar rats. The area under the curve (AUC) and maximum plasma concentration (Cmax) in case of atorvastatin nanoemulsion were found 9-fold and 5-fold higher, respectively when compared to simple atorvastatin suspension. The present study illustrated the potential of nanoemulsion dosage form in improving biopharmaceutic performance of atorvastatin.

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.

The present study was aimed at preparation and performance evaluation of pH-sensitive cyclosporine A (CyA) nanoparticles (CyA-NPs) to improve the poor bioavailability of lipophilic CyA. CyA-NPs were prepared with two types of Eudragit® copolymers (Eudragit ® S100 and Eudragit® L100) by a quasi-emulsion solvent diffusion technique. Freeze-dried formulations (Lac-CyA-S100-NP and Lac-CyA-L100-NP) were also prepared. The physical properties, particle size, encapsulation efficiency, and in vitro drug release characteristics were studied. The in vivo bioavailability of CyA-NP and Lac-CyA-S100-NP was investigated in rats at a dose of 15 mg/kg and compared with that of the commercial formulation, Sandimmune Neoral®. The mean particle size of the CyA-NPs was less than 50 nm, and the encapsulation efficiency was over 99%. Characteristics of the freeze-dried nanoparticles were found to remain relatively stable when lactose was used as a cryoprotectant. In vitro release studies revealed that the CyA-NPs exhibited significant pH-sensitivity. The relative bioavailabilities of CyA-L100-NP, CyA-S100-NP, and Lac-CyA-S100-NP were 117.3%, 162.1%, and 130.1%, respectively, when compared with that of Neoral®. Therefore, CyA-NPs were considered to be promising oral delivery systems for enhancement of the absorption of the poorly soluble drug, CyA. Freeze-dried nanoparticles could be developed into a novel and effective CyA formulations.

Spider silk is intriguing because of its unique structure and high-performance mechanical properties. However, few studies have presented data characterizing the conserved motifs found in the silk protein as an oligopeptide. In this report a designed peptide that mimics the repetitive GGX motif in the silk spidroin was investigated. The peptide undergoes a ‘bottom-up’ self-assembly which was simply manipulated by metal ions and an ionic self-complementary peptide, RADA16-I. In water, the peptide was observed to form discrete and stiff nanorods (PNrs) via hydrophobic interactions. AFM, TEM and DLS data showed that the addition of MgCl2 or CaCl2 led to the formation of a mass of nanorod bundles (PNrs-b). The addition of EDTA forced the disruption of the bundles, therefore providing evidence that the metal ions and peptide interact. Fourier transform infrared spectroscopy showed the presence of coordination bonds bridging the metal ions and the carbonyl groups of the peptide. Such coordination bonds are considered to facilitate the bundling of the nanorods. Conversely, mixing the GGX peptide with the RADA16-I peptide caused a lengthening of the nanorods (L-PNrs). Here, the length of the nanorods changed from several microns to over ten microns. In addition, AFM was used to follow the elongation process. Such a method provided a clear and direct overview of the kinetics of self-assembly.

The investigation of nano-mechanical properties and nano-architectures of CD8 + T cells activated in vitro will help further interpret the immune response/recognition of these cells at nanoscale resolution. In this work, the local biophysical properties of human peripheral blood CD8 + T cells were obtained, revealing the adhesion force of membrane was increased after CD8 + T cells were stimulated with phorbol dibutyrate plus ionomycin, though the measured local stiffness for resting and activated cells was similar. The 3-D distribution pattern and grayscale map together revealed that membrane receptors (CD8 and activation marker CD69) distributed non-uniformly on the membrane and were shown as micro-, nano-scale clusters or domains. This work describes a relatively simple approach for exploiting the distribution pattern of receptor molecules on a single T cell surface.

Zinc metagermanate nanorods have been synthesized by a directly hydrothermal deposition process. The analyses of X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM) indicate that the products are mainly composed of ternary mixed oxide ZnGeO3 with multi-crystalline rhombohedral phase and porous structure. The observation from scanning electron microscopy (SEM) and transmission electron microscopy (TEM) shows that the nanorods have a diameter of 100-600 nm and a length up to 30 μm. Room temperature photoluminescence (PL) spectrum displays that the nanorods have a strong emission band at a wavelength of 400 nm. The proposed growth mechanism is also discussed in the paper.

Flower-like ZnO nanostructures had been successfully synthesized by solvothermal treatment of a precursor 4,5-diphenyloxazole- 2-propanoic acid-zinc (abbreviated as oxaprozin-Zn) complex without using any surfactants. The influence of basicity, temperature, and reaction time on the formation of such structures was investigated. Room-temperature photoluminescence spectrum of welldefined uniform ZnO nanoflowers was investigated. The results indicated that the choice of a precursor could have significant influence on the growth of ZnO nanostructures. This type of complex could be used to prepare other oxdinations with special morphology, suah as CdO and CuO.

A double-tube vapor phase transport system has been used to grow ZnO nanostructures. Nanopillars, nanorods and nanowires of zinc oxide were synthesized on Au nanoparticle catalyst depending on source-substrate distance and temperature gradient in the quartz tube. In addition, influence of growth time and substrate temperature on the morphology of the nanorods and nanowires were also investigated. The scanning electron microscope (SEM), X-ray diffraction (XRD) and transmission electron microscopy (TEM) were employed to further understand the nanostructures growth mechanism on various temperatures and growth time steps. Longer length (>4μm) with hexagonal-cross-sectional nanowires, in [002] growth orientation, were synthesized at low temperatures (875-857°C); while a middle length (<3μm) nanorods were formed at intermediate temperatures (893-875°C). Nanopillars and other irregular nanostructures were also synthesized on the surface at higher temperatures (910-893°C). Based on the TEM observations, the vapor-liquid-solid (VLS) growth mechanism is applied to describe the growth processes for the synthesized nanostructures.

Nanoporous Fe3O4 magnetic microspheres have been successfully synthesized by the way of microwave heating. The experimental process is expeditious, simple and environmentally friendly. The obtained sample is characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Brunauer-Emmett-Teller analysis (BET), Fourier transform infrared (FT-IR), high-resolution transmission electron microscopy (HRTEM) and magnetic measurements. The average size of Fe3O4 microspheres is ∼100nm and shows well-dispersed quality in aqueous solution. More importantly, the microspheres possess both nanoporous structure and superparamagnetic behaviour, which endow them powerful application potentials in chemical, biological/biomedical, physical and environmental engineering fields, for example, catalyst or drug carrier, absorption, separation and contrast agents, etc.

In this research fabrication of crystalline PbZrO3 (PZ) nanoparticles and their phase transformation behavior is investigated. A novel sol-gel method was used for the synthesis of air-stable and precipitate-free diol-based sol of PZ, which was dried at 150 °C and then calcined at 300-700°C for 1 h. The morphology, crystallinity and phase formation of as synthesized nanoparticles were studied by the selected-area electron diffraction (SAED), X-ray diffraction (XRD), thermal gravimetric analysis/differential scanning calorimetry (TGA-DSC), and high resolution transmission electron microscope (HRTEM). The XRD, SAED, and TGA-DSC analyses confirmed the tetragonal lead rich zirconia phase (t-Z phase) and monoclinic zirconia phase (m-Z phase) as the intermediate phases during the calcinations process followed by crystallization of single orthorhombic PZ phase at about 700 oC. The average PZ particle size was observed about 20 nm as confirmed by TEM study. Energy-dispersive X-ray spectroscopy (EDX) analysis demonstrated that stoichiometric PbZrO3 was formed.

In order to improve the wear resistance and oxidation behaviors of Ti-6Al-4V alloy, the sputter-deposited nanocrystalline Cr3Si film was prepared on Ti-6Al-4V alloy substrate by double cathode glow discharge. The nanocrystalline film was characterized by using a variety of analytical techniques, such as XRD, SEM, TEM, scratch tester, nanoindentation and Vickers microhardness tester. The phase analysis results showed that the sputter-deposited Cr3Si film (thickness 8μm) was comprised of equiaxed nanocrystalline Cr3Si with a grain size of less than 5 nm. The nanohardness of the nanocrystalline Cr3Si was 2.37 times higher than that of coarse-grained Cr3Si, whereas the elastic modulus of nanocrystalline Cr3Si was approaching to that of coarse-grained Cr3Si. The critical load value obtained by scratch testing of the nanocrystalline Cr3Si film on Ti-6Al-4V alloy substrate was 80N, confirming that the nanocrystalline Cr3Si film was well adhered to Ti-6Al-4V alloy substrates. Results of cyclic oxidation testing at 700°C and 800°C in air showed that the oxidation kinetic curves of the nanocrystalline Cr3Si film obeyed a parabolic rate law, and oxide scale was mainly comprised of Cr2O3 and amorphous SiO2 with the thickness of < 1μm that could effectively retard the diffusion of oxygen into the nanocrystalline Cr3Si film. The dry wear test results showed that specific wear rate of nanocrystalline Cr3Si film was two order magnitude smaller than that of Ti- 6Al-4V alloy at RT and 500°C.

Small carbon nanocrystal particle (C20, C24, C26) series, synthesized in an ultrahigh molecular weight polyethylene target by C2 + ion beam irradiation, were studied with respect to their micro structures and sequential growth features. As the samples were examined by laser desorption Time-of-flight mass spectroscopy, relative intensive peaks in the spectrum indicated the presence of C20, C24, C26 carbon clusters. High resolution transmission electron microscopy images and electron diffraction patterns showed that the C20, C24 and C26 assembled into nanocrystal particles. Raman scattering spectrum and Fourier transform infrared spectrum analyses also indicated that the active bonds of small carbon cages were hydrogenated, thus the C20, C24, C26 nanocrystal were formed. Additionally, the sequential growth of C20→C22→C24→C26→...with addition of C2 carbon units was found, which provides a novel and efficient approach to synthesize small hydro-fullerenes and their nanocrystal materials.

Novel conducting nanostructured carbonaceous materials of various microstructures have been successfully prepared from nanocomposites containing polyacrylonitrile (PAN) inside the nanosized pores of imogolite, sepiolite and porous alumina membrane templates. The synthesis and electrochemical characterization of the PAN-inorganic porous solid nanocomposites, as well as their carbonaceous derivatives produced after removal of the matrix, have been studied by CHN elemental chemical analysis, thermal analysis (TGDTA), specific surface area and porosity determinations (N2 isotherms), X-ray diffractometry, FTIR, Small-Angle X-ray Scattering (SAXS), SEM, TEM and Electrochemical Impedance Spectroscopy (EIS). The properties of the carbonaceous materials as electroactive materials in electrochemical devices such as rechargeable Li-ion batteries and Electrochemical Double-Layer Capacitors (EDLC) are reported. The main objective of this work is to study the influence of the template used for the preparation of different carbonaceous materials on their physical-chemical characteristics as well as their electrochemical properties, including their behaviour as electrode materials for Li-ion batteries and EDLC capacitors.

Chemical compounds are often modeled as polygonal shapes, where a vertex represents an atom and an edge symbolizes a bond. Topological properties of molecular graphs of chemical compounds can be correlated to their chemical properties and biological activities. Topological indices are the oldest and the most widely used to describing these activity relationships. Many topological indices can be expressed in terms of the distance concept in graphs. In this paper we explain a method, using the concept of distance in the graphs of zigzag polyhex nanotubes, which enables us to compute different topological indices simultaneously.

Nanoliter droplet formation in a confined T-shaped junction is analyzed in detail in virtue of an experimental visualization system with a high speed camera. The movement of the back interface of the tip of disperse phase penetrated into the continuous phase plays an important role in determining droplet formation time and droplet volume. A simple model of droplet formation time based on the analysis of droplet formation process is developed. Influences of continuous phase viscosity and interfacial tension on droplet formation time and droplet volume are concluded in terms of capillary number together with the mean velocity of continuous phase. It is found that both the capillary number and the flow rate ratio of disperse phase to continuous phase have strong impacts on determining droplet volume. Two empirical equations are derived from the model for predicting droplet formation time and droplet volume, respectively.

We present the experimental evidence of substantial increases in fluid thermal conductivity (up to 139%) by adding some fluids even with lower conductivity. This leads to a new type of thermal-wave fluids that could serve as heat transfer fluid of the future much better than recently-proposed nanofluids.