There is a trend in pharmaceutical research and development to develop depot formulations with dosing once weekly, once monthly, or even less frequently. A novel approach to achieve long acting injectable suspensions is to produce dense inorganic nanoshells with atomic layer deposition (ALD) on active pharmaceutical ingredients. Such particles can be suspended in an aqueous vehicle and administered subcutaneously. The purpose of this work was to study the release of a model drug, indomethacin, coated with aluminium oxide nanoshells. Indomethacin was ball-milled to a median particle size of 6 mu m. The nanoshells were produced with a proprietary ALD process that is trademarked as PharmaShell (R) by Nanexa AB. The drug load was determined with HPLC-UV to 82 wt%. The test materials were administered subcutaneously in rats (1, 10, and 100 mg/kg) from which blood samples were collected during 12 weeks. Plasma was generated and analyzed with regards to indomethacin using UPLC-MS/MS. The release rate was dramatically slower for the nanoshell coated indomethacin compared with uncoated indomethacin. Drug was released in vivo during more than 12 weeks for the 10 and 100 mg/kg doses, and during 10 weeks for the 1 mg/kg dose, while uncoated indomethacin was eliminated with a half-life of 15 h, as calculated from the release data by fitting a one phase decay function. The exposure levels were similar as earlier reported for therapeutic indomethacin doses, but significantly sustained in the present study using coated drug particles in rats. In conclusion, this is the first long-term in vivo evaluation of nanoshell depot formulations. The stable plasma concentrations for more than 12 weeks demonstrate that nanoshells can enable long-term depot injections with high drug load.

Atomic layer deposition (ALD) enables deposition of dense nanometer thick metal oxide nanoshells on powder particles with precise thickness control. This leads to products with low weight fraction coating, also when depositing on nano- or micron sized powder particles. This study aimed at investigating the aluminium oxide nanoshell thickness required to prevent moisture sorption. The nanoshells were produced with ALD on spray-dried lactose, which is amorphous and extremely hygroscopic. The particles were studied with dynamic vapor sorption between 0 and 50% RH, light scattering, scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and polarized light microscopy. The ALD did not induce any recrystallization of the amorphous lactose. The dynamic vapor sorption indicated that the moisture sorption was almost completely inhibited by the nanoshell. Neat amorphous lactose rapidly recrystallized upon moisture exposure. However, only ca. 15% of the amorphous lactose particles recrystallized of a sample with 9% (by weight) aluminium oxide nanoshell at storage for six months upon 75% RH/40°C, which indicate that the moisture sorption was completely inhibited in the majority of the particles. In conclusion, the aluminium oxide nanoshells prevented moisture sorption and dramatically improved the long term physical stability of amorphous lactose. This shows the potential of the ALD-technique to protect drug microparticles.

In this work Al2O3 and SiO2 coatings are tested as Xe diffusion barriers on plastic scintillator substrates. The motivation is improved beta–gamma coincidence detection systems, used to measure atmospheric radioxenon within the verification regime of the Comprehensive Nuclear-Test-Ban Treaty. One major drawback with the current setup of these systems is that the radioxenon tends to diffuse into the plastic scintillator material responsible for the beta detection, resulting in an unwanted memory effect. Here, coatings with thicknesses between 20 and 900nm have been deposited onto plastic scintillators, and investigated using two different experimental techniques. The results show that all tested coatings reduce the Xe diffusion into the plastic. The reduction is observed to increase with coating thickness for both coating materials. The 425nm Al2O3 coating is the most successful one, presenting a diffusion reduction of a factor 100, compared to uncoated plastic. In terms of memory effect reduction this coating is thus a viable solution to the problem in question.

A nanostructured three-dimensional (3D) microbattery has been produced and cycled in a Li-ion battery. It consists of a current collector of aluminum nanorods, a uniform layer of 17 nm TiO(2) covering the nanorods made using ALD, an electrolyte and metallic lithium counter electrode. The battery is electrochemically cycled more than 50 times. The increase in total capacity is 10 times when using a 3D architecture compared to a 2D system for the same footprint area.

Double- and triple-walled TiO2/iron oxide nanotubes with well defined interfaces have been produced in nanoporous alumina templates using atomic layer deposition method. The structural properties of each individual layer are found to be dependent on the deposition temperatures. The outer layers of TiO2 are polycrystalline and consist of a phase mixture of anatase and rutile, while the inner TiO2 layers grown at lower temperature are amorphous. The iron oxide layers consist of pure hematite when deposited at 500 °C, while a phase mixture of hematite and magnetite was obtained at 400 °C. The magnetization measurements reveal that the studied nanotubes exhibit weak ferromagnetic behavior and magnetic anisotropy with an easy axis perpendicular to the tube axis.

Thin films of cobalt oxide, iron oxide and niobium oxide, and nanostructured thin films of iron oxide, titanium oxide and multilayered iron oxide/titanium oxide have been deposited by Atomic Layer Deposition (ALD). The metal oxides were grown using the precursor combinations CoI2/O2, Fe(Cp)2/O2, NbI5/O2 and TiI4/H2O. The samples were analysed primarily with respect to phase content, morphology and growth characteristics.Thin films deposited on Si (100) were found to be amorphous or polycrystalline, depending on deposition temperature and the oxide deposited; cobalt oxide was also deposited on MgO (100), where it was found to grow epitaxially with orientation (001)[100]Co3O4||(001)[100]MgO. As expected, the polycrystalline films were rougher than the amorphous or the epitaxial films. The deposition processes showed properties characteristic of self-limiting ALD growth; all processes were found to have a deposition temperature independent growth region. The deposited films contained zero or only small amounts of precursor residues.The nanostructured films were grown using anodic aluminium oxide (AAO) or carbon nanosheets as templates. Nanotubes could be manufactured by depositing a thin film which covers the pore walls of the AAO template uniformly; free-standing nanotubes retaining the structure of the template could be fabricated by removing the template. Multilayered nanotubes could be obtained by depositing multiple layers of titanium dioxide and iron oxide in the pores of the AAO template. Carbon nanosheets were used to make titanium dioxide nanosheets with a conducting graphite backbone. The nucleation of the deposited titanium dioxide could be controlled by acid treatment of the carbon nanosheets.

A non-bioactive implant device can easily be changed to in vitro bioactive with a thin coating of crystalline TiO2. This crystalline coating can be deposited very thin with great step coverage at a low temperature with Atomic Layer Deposition (ALD). An anatase TiO2 coating was built up atomic layer by atomic layer using TiI4 and H2O as precursors in a hot wall furnace. Several hundreds of cycles resulted in a 10-30nm well defined TiO2 of anatase phase on both Si and Ti substrates. These coatings were shown to be bioactive when immersed in simulated body fluid in vitro, as hydroxyapatite (HA) formed on the surface. The surface roughness of the substrates affected the adhesion of the HA. The adhesion was low on the smooth Si but much better on the 100 times rougher Ti. The ALD technique is promising for coating substrates of all shapes with bioactive crystalline TiO2 at a low temperature.

Thin films and nanotubes of iron oxide are deposited using atomic layer deposition (ALD) on Si(100) and anodic aluminum oxide (AAO), respectively. Ferrocene, Fe(Cp)(2), and oxygen are used as precursors. Successful depositions are carried out in the temperature range 350-500 degrees C on Si(100), while all depositions on AAO are made at 400 degrees C. The growth per cycle values are around 0.14 nm on Si(100) in the temperature range 350-500 degrees C and 0.06 nm on AAO. Below 500 degrees C, the iron oxide crystallizes as a phase mixture on both types of substrates. One of the phases is identified as the rhombohedral Fe2O3 phase (hematite), but the second phase cannot be unambiguously identified. Above 500 degrees C, only phase pure hematite is detected. For deposition of nanotubes, in-house made AAO membranes are used, having an aspect ratio of 30. By etching of the AAO membranes after deposition, free-standing nanotubes retaining the order of the AAO template can be fabricated.

Nanostructured films of anatase TiO2 is deposited on carbon nanosheet (CNS) templates using atomic layer deposition (ALD). The high-surface area of the CNS together with the unique step coverage of the ALD process makes it possible to obtain sheet-like TiO2 nanostructures, for use in potential applications, e.g. photocatalysis and photovoltaics. A problem with ALD on CNS was the low nucleation rate giving TiO2 films with pinholes. It is shown that introduction of defects by an acid-treatment process can be used to control initial nucleation and growth of the films. The TiO2 on the defect-rich CNS nucleates faster and results in a film with no observable pinholes consisting of crystalline grains in an amorphous matrix.

Hafnium oxide films with a measured relative dielectric constant of 15.4 were deposited at room temperature on Si and 4H-SiC substrates, as well as on 4H-SiC p-i-n diodes. An 8 nm thick SiO2 interfacial layer on SiC increased the breakdown field of the HfO2∕SiO2 stack by 6%, while a 13 nm thick SiO2 layer reduced it by 35%. The evidence of different current conduction mechanisms in SiO2 is shown to be related to the oxide thickness. For the diodes, the breakdown voltage was extended by at least 20%, compared to nonpassivated devices. Annealing at 400 °C in a forming gas changed the crystallinity and increased the relative dielectric constant of the HfO2 layers. There is an indication of reaction between HfO2 and SiO2 in the stacked films after annealing.

Thin films Of Co3O4 have been successfully deposited on SiO2/Si(100) and MgO(001) substrates by atomic layer deposition (ALD) using the precursor combination CoI2/O-2. The deposition temperature was found to have a strong influence on the growth rate. On SiO2/Si(100) substrates, growth rates of about 0.2 nm per cycle were recorded at 500 degrees C, decreasing to 0.004 nm per cycle at 700 degrees C. Oil MgO(001) substrates the growth rates were lower, reaching about 0.12 nm per cycle at 475 degrees C, while no growth could be detected at 700 degrees C. The films were found to grow as the cubic Co3O4 phase throughout the temperature range 475-700 degrees C, polycrystalline on SiO2/Si(100), and epitaxial on MgO(001). On MgO(001) the epitaxial relationship was established to the in-plane orientation (001)[100](Co3O4)parallel to(001)[100](MgO). No iodine could be detected by Rutherford backscattering spectroscopy (RBS) or by X-ray fluorescence (XRF) spectroscopy in any of the deposited films.

This work examines the structural and electrical properties of HfSixOy film based metal-insulator-semiconductor capacitors by means of x-ray diffraction, x-ray photoelectron spectroscopy, capacitance-voltage (C-V), deep level transient spectroscopy, and conductance transient (G-t) techniques. Hafnium-rich silicate films were atomic layer deposited onto HF-etched or SiO2 covered silicon. Although as-deposited samples exhibit high interfacial state and disorder-induced gap state densities, a postdeposition thermal annealing in vacuum under N2 flow for 1min at temperatures between 600 and 730°C clearly improves the interface quality. Marked crystallization and phase separation occurred at 800°C, increasing the structural heterogeneity and defect density in the dielectric oxide layers.

Amorphous niobium oxide (Nb 2 O 5 ) nano-tubes were fabricated inside anodic alumina templates using atomic layer deposition (ALD). The nanoporous templates were in-house fabricated anodic alumina membranes having an inter-pore distance of about 100 nm with pores lengths of 2 µm. The pores were parallel and well ordered in a hexagonal pattern. Atomic layer deposition was performed using gas pulses of niobium iodide (NbI 5 ) and oxygen separated by purging pulses of argon. By employing long gas pulses (30 s) it was possible to get coherent and amorphous Nb 2 O 5 films conformally covering the pore-walls of the alumina template. The outer diameter of the nano-tubes was tailored between 40 and 80 nm by using alumina templates with different pore sizes. By using template membranes with pores not opened in the bottom, nano-tubes with one side closed could be fabricated. Free-standing, and still parallel, nano-tubes could be obtained by selectively etching away the alumina template using phosphoric acid. Using the above mentioned procedure it was possible to fabricate unsurpassed parallel niobium oxide nano-tubes of equal length, diameter and wall-thickness, ordered in a perfect hexagonal pattern. The samples were analysed using high resolution scanning electron microscopy (HR-SEM), transmission electron microscopy (TEM), electron diffraction and x-ray fluorescence spectroscopy (XRFS).