There is an urgent need for novel inhalable drug carriers to fight respiratory infections. Lipid-coated mesoporous silica particles (LC-MSPs) combine the biocompatibility of lipids with the aerosolization properties of micronized low-density MSPs. In this study, the abundant lung surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) was used to coat disordered MSPs by means of two methods: vesicle fusion (VF) and spray-drying (SD). FT-IR and TGA analyses indicated the presence of the lipid coating, while SEM images revealed spherical particles with a smooth, homogenous surface and no detectable lipid aggregates. Both the VF and SD methods resulted in full phospholipid coverage on the outer silica surface (>100 %). However, the VF method produced a more homogeneous coating across particles and achieved a higher lipid content compared to SD (7.0 vs 3.0 % w/w). The resulting LC-MSPs exhibited favorable aerosolization properties, enabling efficient pulmonary delivery of clofazimine, a lipophilic antitubercular drug. The DPPC coating promoted interaction with endogenous lung surfactant, which enhanced the dispersion of the particles in the alveolar environment and significantly increased drug dissolution (from 35 to 75 %). Lipid coating significantly enhances particle adhesion and penetration across the human bronchial mucus layer and into the underlying tissue. Overall, our study presents a refined formulation strategy using phospholipid-coated MSPs as a single-component dry powder carrier, offering targeted lung deposition, enhanced drug dissolution, mucoadhesion, and tissue penetration.

Pulmonary delivery and formulation of biologics are among the more complex and growing scientific topics in drug delivery. We herein developed a dry powder formulation using disordered mesoporous silica particles (MSP) as the sole excipient and lysozyme, the most abundant antimicrobial proteins in the airways, as model protein. The MSP had the optimal size for lung deposition (2.43 +/- 0.13 mu m). A maximum lysozyme loading capacity (0.35 mg/mg) was achieved in 150 mM PBS, which was seven times greater than that in water. After washing and freeze-drying, we obtained a dry powder consisting of spherical, non-aggregated particles, free from residual buffer, or unabsorbed lysozyme. The presence of lysozyme was confirmed by TGA and FT-IR, while N2 adsorption/desorption and SAXS analysis indicate that the protein is confined within the internal mesoporous structure. The dry powder exhibited excellent aerodynamic performance (fine particle fraction <5 <mu>m of 70.32%). Lysozyme was released in simulated lung fluid in a sustained kinetics and maintaining high enzymatic activity (71-91%), whereas LYS-MSP were shown to degrade into aggregated nanoparticulate microstructures, reaching almost complete dissolution (93%) within 24 h. MSPs were nontoxic to in vitro lung epithelium. The study demonstrates disordered MSP as viable carriers to successfully deliver protein to the lungs, with high deposition and retained activity.

The potential of micron-sized amorphous mesoporous silica particles as a novel controlled release drug delivery system for pulmonary administration has been investigated. Mesoporous silica formulations were demonstrated to provide a narrower particle size distribution and (spherical) shape uniformity compared to commercial micronized formulations, which is critical for repeatable and targeted aerosol delivery to the lungs. The release profiles of a well-known pulmonary drug loaded into mesoporous particles of different mean particle diameters (2.4, 3.9 and 6.3 µm) were analysed after aerosolization in a modified Andersen Cascade Impactor. Systematic control of the release rate of drug loaded into the particles was demonstrated in simulated lung fluid by variation of the mean particle diameter, as well as an enhanced release compared to a commercial micronized formulation. The mesoporous silica formulations all demonstrated an increased release rate of the loaded drug and moreover, under aerosolization from a commercial, low-cost dry powder inhaler (DPI) device, the formulations showed excellent performance, with low retainment and commercially viable fine particle fractions (FPFs). In addition, the measured median mass aerodynamic diameter (MMAD) of the different formulations (2.8, 4.1 and 6.2 µm) was shown to be tuneable with particle size, which can be helpful for targeting different regions in the lung. Together these results demonstrate that mesoporous silica formulations offer a promising novel alternative to current dry powder formulations for pulmonary drug delivery.

Inhalation therapy treating severe infectious disease is among the more complex and emerging topics in controlled drug release. Micron-sized carriers are needed to deposit drugs into the lower airways, while nano-sized carriers are of preference for cell targeting. Here, we present a novel and versatile strategy using micron-sized spherical particles with an excellent aerodynamic profile that dissolve in the lung fluid to ultimately generate nanoparticles enabling to enhance both extra- and intra-cellular drug delivery (i.e., dual micro-nano inhalation strategy). The spherical particles are synthesised through the condensation of nano-sized amorphous silicon dioxide resulting in high surface area, disordered mesoporous silica particles (MSPs) with monodispersed size of 2.43 μm. Clofazimine (CLZ), a drug shown to be effective against multidrug-resistant tuberculosis, was encapsulated in the MSPs obtaining a dry powder formulation with high respirable fraction (F.P.F. <5 μm of 50%) without the need of additional excipients. DSC, XRPD, and Nitrogen adsorption-desorption indicate that the drug was fully amorphous when confined in the nano-sized pores (9–10 nm) of the MSPs (shelf-life of 20 months at 4 °C). Once deposited in the lung, the CLZ-MSPs exhibited a dual action. Firstly, the nanoconfinement within the MSPs enabled a drastic dissolution enhancement of CLZ in simulated lung fluid (i.e., 16-fold higher than the free drug), increasing mycobacterial killing than CLZ alone (p = 0.0262) and reaching concentrations above the minimum bactericidal concentration (MBC) against biofilms of M. tuberculosis (i.e., targeting extracellular bacteria). The released CLZ permeated but was highly retained in a Calu-3 respiratory epithelium model, suggesting a high local drug concentration within the lung tissue minimizing risk for systemic side effects. Secondly, the micron-sized drug carriers spontaneously dissolve in simulated lung fluid into nano-sized drug carriers (shown by Nano-FTIR), delivering high CLZ cargo inside macrophages and drastically decreasing the mycobacterial burden inside macrophages (i.e., targeting intracellular bacteria). Safety studies showed neither measurable toxicity on macrophages nor Calu-3 cells, nor impaired epithelial integrity. The dissolved MSPs also did not show haemolytic effect on human erythrocytes. In a nutshell, this study presents a low-cost, stable and non-invasive dried powder formulation based on a dual micro-nano carrier to efficiently deliver drug to the lungs overcoming technological and practical challenges for global healthcare.

Optimization of boundary lubrication by tuning the confined molecular structures formed by surface-active additives such as surfactants and polymers is of key importance to improving energy efficiency in mechanical processes. Here, using the surface forces apparatus (SFA), we have directly measured the normal and shear forces between surface layers of a functionalised olefin copolymer (FOCP) in n-dodecane, deposited onto mica using the Langmuir-Blodgett (LB) technique. The FOCP has an olefin backbone decorated with a statistical distribution of polar-aromatic groups, with a structure that we term as "centipede". The effect of lateral confinement, characterised by the surface pressure, Pi(dep), at the air-water interface at which the LB films are transferred, was examined. Normal force profiles revealed that the thickness of the LB films increased significantly with Pi(dep), with the film thickness (t > 20 nm) inferring a multi-layered film structure, consistent with the interfacial characterisation results from synchrotron X-ray reflectivity (XRR) measurements. The coefficient of friction, mu, between the LB films spanned two orders of magnitude from superlubricity (mu similar to 0.002) to much higher friction (mu > 0.1) depending nonlinearly on Pi(dep), with the lowest friction observed at the intermediate Pi(dep). Molecular arrangement upon LB compression leads to the multilayer film with a structure akin to an interfacial gel, with transient crosslinking facilitated by the intra- and inter-molecular interactions between the functional groups. We attribute the differences in frictional behaviour to the different prevalence of the FOCP functional groups at the lubricating interface, which depends sensitively on the degree of compression at the air-water interface prior to the LB deposition. The LB films remain intact after repeated compression (up to pressures of 10 MPa) and shear cycles, indicating strong surface anchorage and structural robustness as a load-bearing and shear-mediating boundary layer. These unprecedented results from the friction measurements between LB films of a statistical copolymer in oil point towards new strategies for tailoring macromolecular architecture for mediating efficient energy dissipation in oil-based tribological applications.

Neutrons are characterized by a low absorption in many engineering materials. At the same time the scattering cross section of light elements, such as hydrogen and deuterium, may be large. These properties make neutron scattering experiments performed under grazing incidence geometry an excellent tool for the study of solid–liquid interfaces. In this review we describe the basic concepts of neutron reflection and grazing incidence scattering experiments as well as experimental procedures and sample cells. The full power of the method is exemplified on a range of science areas, including polymers, bio- and ionic liquid lubricants, electrolytes as well as bio-membranes or magnetic liquids.

The structure and interaction of ionic liquids (ILs) influence their interfacial composition, and their arrangement (i.e., electric double-layer (EDL) structure), can be controlled by an electric field. Here, we employed a quartz crystal microbalance (QCM) to study the electrical response of two non-halogenated phosphonium orthoborate ILs, dissolved in a polar solvent at the interface. The response is influenced by the applied voltage, the structure of the ions, and the solvent polarizability. One IL showed anomalous electro-responsivity, suggesting a self-assembly bilayer structure of the IL cation at the gold interface, which transitions to a typical EDL structure at higher positive potential. Neutron reflectivity (NR) confirmed this interfacial structuring and compositional changes at the electrified gold surface. A cation-dominated self-assembly structure is observed for negative and neutral voltages, which abruptly transitions to an anion-rich interfacial layer at positive voltages. An interphase transition explains the electro-responsive behaviour of self-assembling IL/carrier systems, pertinent for ILs in advanced tribological and electrochemical contexts.

The effect of electric potential on the lubrication of a non-halogenated phosphonium orthoborate ionic liquid used as an additive in a biodegradable oil was studied. An in-house tribotronic system was built around an instrument designed to measure lubricant film thickness between a rolling steel ball and a rotating silica-coated glass disc. The application of an electric field between the steel ball and a set of customized counter-electrodes clearly induced changes in the thickness of the lubricant film: a marked decrease at negative potentials and an increase at positive potentials. Complementary neutron reflectivity studies demonstrated the intrinsic electroresponsivity of the adsorbate: this was performed on a gold-coated silicon block and made possible in the same lubricant system by deuterating the oil. The results indicate that the anions, acting as anchors for the adsorbed film on the steel surface, are instrumental in the formation of thick and robust lubricating ionic boundary films. The application of a high positive potential, outside the electrochemical window, resulted in an enormous boost to film thickness, implicating the formation of ionic multi-layers and demonstrating the plausibility of remote control of failing contacts in inaccessible machinery, such as offshore wind and wave power installations.

Four nonhalogenated ionic liquids (ILs) based on the same phosphonium cation are investigated in terms of the anion suitability for enhancing the lubricity of a biodegradable oil. For all test conditions, typical for industrial machine components, the lubrication is shown to be governed by nonsacrificial films formed by the physisorption of ionic species on the tribo-surfaces. The anionic structure appears to have an important role in the formation of friction modifying films. The orthoborate ILs exhibit the formation of robust ionic boundary films, resulting in reduced friction and better wear protection. On the contrary, the surface adsorption of phosphinate and phosphate ILs appears to antagonistically disrupt the intrinsic lubrication properties of the biodegradable oil, resulting in high friction and wear. Through additional investigations, it is postulated that the higher dissociation of orthoborate ILs in the biodegradable oil allows the formation of hierarchical and electrostatically overscreened layer structures with long-range order, whereas the ILs with phosphate and phosphinate anions exhibit low dissociation in biodegradable oil, possibly due to the ion pairs being surrounded by a hydrocarbon halo, which presumably results in weak adsorption to form a mixed interfacial layer with no long-range order.

It is shown that the air-liquid interface can be made to display the same rich curvature phenomena as common lyotropic liquid crystal systems. Through mixing an insoluble, naturally occurring, branched fatty acid, with an unbranched fatty acid of the same length, systematic variation in the packing constraints at the air-water interface could be obtained. The combination of atomic force microscopy and neutron reflectometry is used to demonstrate that the water surface exhibits significant tuneable topography. By systematic variation of the two fatty acid proportions, ordered arrays of monodisperse spherical caps, cylindrical sections, and a mesh phase are all observed, as well as the expected lamellar structure. The tuneable deformability of the air-water interface permits this hitherto unexplored topological diversity, which is analogous to the phase elaboration displayed by amphiphiles in solution. It offers a wealth of novel possibilities for the tailoring of nanostructure.