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Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pK

Oral transmucosal drug delivery is a non-invasive administration route for rapid therapeutic onset and greater bioavailability avoiding the first-pass metabolism. Mucoadhesive formulations are advantageous as they may retain the drug at the administration site. Proper equipment to assess mucoadhesive properties and corresponding drug absorption is fundamental for the development of novel drug delivery systems. Here we developed a new flow-through donor chamber for well-established diffusion cells, and we tested the effects on drug and formulation retention in situ of adding mucoadhesive polymers or mesoporous silica particles to a reference formulation. Mesoporous silica particles are of particular interest as they may be used to encapsulate and retain drug molecules. Compared to other ex-vivo methods described in literature for assessing mucoadhesive performance and transmucosal drug delivery, this new donor chamber provides several advantages: i) it reflects physiological conditions better as a realistic saliva flow can be provided over the administration site, ii) it is versatile since it can be mounted on any kind of vertical diffusion cell allowing simultaneous detection of drug retention at the administration site and drug permeation through the tissue, and iii) it enables optical quantification of formulations residence time aided by image processing. This new flow-through donor diffusion cell set-up proved sensitive to differentiate a reference formulation from one where 20 %(w/w) Carbomer was added (to further improve the mucoadhesive properties), with respect to both drug and formulation residence times. We also found that mesoporous silica particles, investigated as particles only and mixed together with the reference formulation, gave very similar drug and formulation retention to what we observed with the mucoadhesive Carbomer. However, after some time (>30 min) it became obvious that the tablet excipients in the reference formulation promote particle retention on the mucosa. This work provides a new simple and versatile biorelevant test for the evaluation of oral mucoadhesive formulations and paves the way for further studies on mesoporous silica particles as valuable excipients for enhancing oral mucoadhesion.

Cyclodextrins (CDs) and mesoporous silica particles (MSPs) have been combined as composite carriers for controlled antibiotic release. CDs were employed as "gatekeeper" agents and grafted onto MSPs to retain drug molecules inside the MSP carrier. A variety of CDs (unfunctionalized, positively charged and carboxymethylated) and three different coupling strategies (covalent binding, electrostatic adsorption and inclusion complexation) were systematically investigated for their ability to control the release of two antibiotic drugs, metronidazole and clofazimine. The drugs had significantly different physicochemical properties (metronidazole - small hydrophilic, clofazimine- large hydrophobic). We report for the first time on the encapsulation and characterization of metronidazole-loaded-MSP. Each CD coating strategy reduced the drug release rate in phosphate buffer compared to unmodified MSP (from 20% to 100% retained drug). Covalent binding and inclusion complex approaches were significantly more effective than electrostatically adsorbed CD. In particular, the novel inclusion complex based on host/guest interaction between benzyl-modified silica surface and α-CD proved to be very effective (60-100% retained drug amount). Using pharmaceutical manufacturing processes, our study shows that CD-MSP composites can retain both hydrophobic and hydrophilic antibiotic compounds with potential translation to triggered release formulation targeting bacterial infections in the colon and lower intestine.

We develop and combine a novel numerical model, within the Poisson-Boltzmann framework, with classical experimental titration techniques for mesoporous silica particles to study the charging behavior as both pH and the amount of monovalent salt are varied. One key finding is that these particles can be considered to have an effectively or apparent electroneutral inner core with an effectively charged rim. As a consequence, the total apparent charge of the particle is several orders of magnitude smaller than that of the bare silica charge, which accounts only for the charged silanol groups of the mesoporous silica particles and which has its major contribution from the interior. Hence, the interior dictates the mesoporous silicas' bare charge while the rim its effective charge. We furthermore report density, charge, and accumulated charge profiles across the particle's interface.

A mesoporous silica material prepared by using folic acid (FA) as a template enables the effective encapsulation of meso-tetrakis(4-carboxyphenyl) porphyrin (TCPP) in its interior. Combination of steady-state and time-resolved absorption and emission spectroscopy demonstrate that FA and TCPP are released from the silica material to the aqueous phase in the form of a non-covalent assembly. This assembly does not form by simple mixing of the two components in the absence of silica, suggesting the key role of the material in the assembling process. The FA/TCPP assembly exhibits dual color fluorescence in the visible region, good photosensitization capability of singlet oxygen, and enhanced photo-induced mortality in KB cancer cells overexpressing folate receptor, if compared with the free components. QC 20170620

Aim: First extensive reformulation of clofazimine (CLZ) in nanoporous silica particles (NSPs) for tackling antibiotic-resistant tuberculosis (TB) infections. Materials & methods: Solid-state characterization of several CLZ-encapsulated NSP formulations was followed by in vitro drug solubility, Caco-2 intestinal cells drug permeability and TB antibacterial activity. Results: NSPs stabilize the amorphous state of CLZ (shelf stability >6 months) and dramatically increase the drug solubility in simulated gastric fluid (up to 20-fold) with different dissolution kinetics depending on the NSPs used. CLZ encapsulation in NSP substantially enhances the permeation through model intestinal cell layer, achieving effective antimicrobial concentrations in TB-infected macrophages. Conclusion: Promising results toward refurbishment of an approved marketed drug for a different indication suitable for oral anti-TB formulation.

Amyotrophic lateral sclerosis (ALS) is a devastating incurable neurological disorder characterized by motor neuron (MN) death and muscle dysfunction leading to mean survival time after diagnosis of only 2–5 years. A potential ALS treatment is to delay the loss of MNs and disease progression by the delivery of trophic factors. Previously, we demonstrated that implanted mesoporous silica nanoparticles (MSPs) loaded with trophic factor peptide mimetics support survival and induce differentiation of co-implanted embryonic stem cell (ESC)-derived MNs. Here, we investigate whether MSP loaded with peptide mimetics of ciliary neurotrophic factor (Cintrofin), glial-derived neurotrophic factor (Gliafin), and vascular endothelial growth factor (Vefin1) injected into the cervical spinal cord of mutant SOD1 mice affect disease progression and extend survival. We also transplanted boundary cap neural crest stem cells (bNCSCs) which have been shown previously to have a positive effect on MN survival in vitro and in vivo. We show that mimetic-loaded MSPs and bNCSCs significantly delay disease progression and increase survival of mutant SOD1 mice, and also that empty particles significantly improve the condition of ALS mice. Our results suggest that intraspinal delivery of MSPs is a potential therapeutic approach for the treatment of ALS.

When applied to skin, particulate matter has been shown to accumulate in hair follicles. In addition to follicles, the skin topography also incorporates trench-like furrows where particles potentially can accumulate; however, the furrows have not been as thoroughly investigated in a drug delivery perspective. Depending on body site, the combined follicle orifices cover up to 10% of the skin surface, while furrows can easily cover 20%, reaching depths exceeding 25 µm. Hence, porous particles of appropriate size and porosity could serve as carriers for drugs to be released in the follicles prior to local or systemic absorption. In this paper, we combine multiphoton microscopy, scanning electron microscopy, and Franz cell diffusion technology to investigate ex-vivo skin accumulation of mesoporous silica particles (average size of 400–600 nm, 2, and 7 µm, respectively), and the potential of which as vehicles for topical delivery of the broad-spectrum antibiotic metronidazole. We detected smaller particles (400–600 nm) in furrows at depths of about 25 µm, also after rinsing, while larger particles (7 µm) where located more superficially on the skin. This implies that appropriately sized porous particles may serve as valuable excipients in optimizing bioavailability of topical formulations. This work highlights the potential of skin furrows for topical drug delivery.

Amino-terminated mesoporous silica nanoparticles embedding carbon dots (MSCD) formed by calcination were functionalized with a nitric oxide (NO) photodonor (1) to give a robust MSCD-1 conjugate. The intense fluorescence of MSCDs was strongly quenched in MSCD-1 by effective energy transfer. Visible light excitation of MSCD-1 liberates NO, suppresses the energy transfer mechanism and leads to concomitant fluorescence restoration of the MSCD scaffold, which acts as an optical reporter for the released NO. The MSCD-1 hybrid is also able to encapsulate the highly hydrophobic photosensitizer temoporfin, preserving the fluorescence reporting function.

Three types of new label-free fluorescent mesoporous silica micro- and nanoparticles were prepared by controlled thermal decomposition of carboamino groups linked on the surface without compromising the drug loading capacity of the silica particles. Clofazimine, a lipophilic antibiotic drug with excellent in vitro activity against mycobacterium tuberculosis, was encapsulated inside these fluorescent particles to obtain multifunctional drug carriers of interest in the field of theranostics. The morphological features together with the photophysical properties of both powders and aqueous suspensions are described. The photophysical properties seem to be independent of the mesoporosity features but correlate with the residual carboamino functionalization. The particles are endowed with emission in the visible region and have fluorescence lifetimes of up to 9.0 ns that can be easily discriminated from intrinsic biological fluorescence. Furthermore, their fluorescence lifetime offers a promising tool to follow the release of the encapsulated drug which is not possible by means of simple fluorescence intensity. We report here a novel attractive theranostic platform enabling monitoring of drug release in biological environments by means of fluorescence lifetime. QC 20170530

We report on the encapsulation of the antibiotic clofazimine (CLZ) within the pores of mesoporous silica particles having hydrophilic (CBET value of 137) and more hydrophobic (CBET value of 94 after calcination at 600 °C) surfaces. We studied the effect of pH on the released amount of CLZ in aqueous solutions and observed a maximum at pH 4.1 in correlation with the solubility of the drug. Less release of the drug was observed from the more hydrophobic particles which was attributed to a difference in the affinity of the drug to the carrier particles. Fluorescence lifetime imaging microscopy, emission spectra, and fluorescence lifetimes of single drug loaded particles provided detailed understanding and new knowledge of the physical form of the encapsulated drug and the distribution within the particles. The distribution of CLZ within the particles was independent of the surface chemistry of the particles. The confirmation of CLZ molecules as monomers or aggregates was revealed by controlled removal of the drug with solvent. Additionally, the observed optical "halo effect" in the fluorescent images was interpreted in terms of specific quenching of high concentration of molecules. The emission lifetime experiments suggest stronger interaction of CLZ with the more hydrophobic particles, which is relevant to its release. The results reported in this work demonstrate that tuning the hydrophilicity/hydrophobicity of mesoporous silica particles can be used as a tool to control the release without impacting their loading ability.

The EU has published her Action Plan in 2011 against the rising threats from antimicrobial resistance. Developing new antibiotics is mandatory but takes years. A short-term alternative is the development of novel strategies to deliver existing drugs in an optimized way. In this frame, the use of engineered antibiotic nanocarriers is one of the most promising options. The objective of our research in the frame of the ITN project Cyclonhit is to take full advantage of nanotechnology to efficiently encapsulate antibiotics in nanocarriers to kill both intracellular and extracellular bacteria. We have focused on two drugs, Ethionamide and Clofazimine, used for the treatment of TBC and Lepromatous Leprosy, respectively. Both suffer from very low solubility in water reducing drastically their bioavailability and complicating their administration. We have studied two different types of carrier systems consisting of polymeric cyclodextrins marked with fluorophores, on one hand, and porous fluorescent silica particles with size ranging from few hundreds of nm to 2 micrometers, on the other hand. We will discuss loading of the two drugs by these new fluorescent carrier systems, their antibacterial activity and their penetration in skin tissue.

The present work, using an atomic force microscope and the colloid probe technique, investigates the interaction forces between bovine serum albumin (BSA) layers and between apoferritin layers adsorbed on silica surfaces. The measurements have been carried out in an aqueous medium at different pH values and NaCl concentrations. Similar behaviours have been found with both proteins. Electrostatic and steric forces dominate the interactions between the protein layers at low NaCl concentrations. However, a very strange behaviour is found as a function of pH at high NaCl concentrations. The results obtained under these conditions could be explained if the presence of hydration forces in these systems is assumed.

The interaction forces between bovine serum albumin (BSA) layers adsorbed on silica surfaces have been measured using an atomic force microscope (AFM) in conjunction with the colloid probe technique. Measurements of force−distance curves were made at different pH values and electrolyte concentrations (NaCl and CaCl2). The interaction at long range is dominated by electrical double-layer forces, while at short surface separations an additional repulsion due to the compression of the adsorbed protein layers appears. However, prior to this steric interaction, when the pH is above the isoelectric point of the protein and at high salt concentration, a non-DLVO repulsive interaction is observed. This behavior is explained if the presence of hydration forces in the system is assumed. Theoretical predictions including a hydration term in the DLVO theory fit the experimental results satisfactorily. The results presented in this article provide a direct confirmation that the AFM colloid probe technique can provide ...

By the aid of an atomic force microscope (AFM) and the colloid probe technique, the interaction forces between bovine serum albumin (BSA) layers adsorbed on different substrates (silica and polystyrene) have been measured directly as a function of pH and salt concentration. Electrostatic and steric forces dominate the interactions at low salt concentrations. At high salt concentrations, when electrostatic interactions are screened, a very strange behaviour is found as a function of pH. The behaviour around the i.e.p. of the protein is also very striking: the interaction is attractive at low salt concentration, but it is repulsive at high salt concentration. These results could be explained if the presence of hydration forces is assumed. Theoretical predictions including a hydration term in the DLVO theory fit the experimental results satisfactorily.

The adsorption and frictional properties of gemini surfactants at hydrophilic gold surfaces were measured using QCM-D (quartz crystal microbalance dissipation) and AFM. The molecular packing of a series of gemini surfactants was determined from QCM-D measurements, and the frictional behaviors of the surfactant films were characterized by employing atomic force microscopy (AFM). The results show that by changing the length of the spacer group from 3 to 12 a systematic change in the molecular packing at the surface is obtained. Furthermore, the molecular packing is seen to correlate to the frictional behavior of the surfactant film. A linear relation between the spacer group length, the adsorbed amount, and the frictional properties of the layer at the solid surface is found. This is discussed in terms of the critical packing parameter (CPP) of the surfactant, and a relation between CPP and frictional behavior is proposed. No correlation between spacer length and viscoelasticity of the adsorbed surfactant l...

Friction-force measurements between a silica sphere and a titanium dioxide wafer in electrolyte solutions were made using an atomic force microscope. The effect of electrical double-layer interactions on the adhesion and the friction force were investigated as a function of pH. In contrast to taking friction measurements in air, conducting the study in aqueous solution has allowed the surface separation, adhesion, and applied force to be controlled independently. Friction was found to be dependent only on the intrinsic force. Friction was seen to be independent of pH. When a force law fitted to the measured data was used, the separation as a function of intrinsic force was likewise found by theoretical calculations to be independent of pH. It was concluded that friction was solely dependent on separation and that the effect of applied force and electrical double-layer interactions served merely to change the separation. In addition, it was proposed that a single layer of unbound water molecules effectivel...

A model system comprising of chemically-dissimilar and oppositely-charged metal oxides has been used to investigate the removal of small particles from surfaces and, particularly, the role of interaction forces in this process. Techniques including reflectometry, rheology, microelectrophoresis, acoustophoresis and atomic force microscopy have been utilised. Silica particles adsorbed onto titania surfaces were removed by the addition of phosphate. The phosphate was shown to adsorb selectively to the titania. Desorption of the silica particles has been attributed to the ability of the phosphate to modify the interaction forces between the metal oxides. Phosphate was found to alter the electrostatic force between silica and titania from attractive to repulsive. It also introduced an additional repulsive force, which has been ascribed to the presence of a steric barrier. In addition, significant reductions in the adhesive and frictional forces acting between silica and titania were observed. The implications of the findings for ‘slimes’ control during the separation of mineral ores are discussed.

We present a direct one-step technique to measure the torsional spring constant of cantilevers used for lateral or friction measurements with the atomic force microscope. The method simultaneously calibrates the photodiode response to the angular deflection of the cantilever. It does not rely upon any approximate theory for friction, nor upon any simplified model cantilever geometry or elasticity. The technique is verified by comparison with the calculated spring constant and with an independent measurement of the angle calibration. This nondestructive calibration may be performed with any type of cantilever, and the friction may subsequently be measured with any type of substrate or probe.

An atomic force microscope has been used to study the interaction between silica and titanium dioxide surfaces, in the form of both colloidal particles and flat surfaces, as a function of pH and in the presence of linear polyphosphates. In the absence of polyphosphate, the interaction force between silica and titanium dioxide in both symmetric (silica sphere–silica flat, titanium dioxide sphere–titanium dioxide flat) and asymmetric cases (silica sphere–titanium dioxide flat) was well described by DLVO theory. Independent streaming potential measurements of the titanium dioxide flat surfaces under the same conditions showed excellent agreement with the diffuse layer potentials derived from the force data. In the presence of polyphosphate the interaction force between silica and titanium dioxide was dominated at long range by electrostatic double layer forces and at short range by non-DLVO steric interactions. Both the repulsive electrostatic double layer interaction and the extent of the steric force increased with increasing polyphosphate concentration and n, where n is the number of phosphorus atoms in the molecule. Measurements of the steric layer thickness taken directly from the force data compared extremely well with predictions based on molecular modelling.

Using colloid probe atomic force microscopy, we show that if repulsive van der Waals forces exist between two surfaces prior to their contact then friction is essentially precluded and supersliding is achieved. The friction measurements presented here are of the same order as the lowest ever recorded friction coefficients in liquid, though they are achieved by a completely different approach. A gold sphere attached to an AFM cantilever is forced to interact with a smooth Teflon surface (templated on mica). In cyclohexane, a repulsive van der Waals force is observed that diverges at short separations. The friction coefficient associated with this system is on the order of 0.0003. When the refractive index of the liquid is changed, the force can be tuned from repulsive to attractive and adhesive. The friction coefficient increases as the Hamaker constant becomes more positive and the divergent repulsive force, which prevents solid-solid contact, gets switched off.

Mesoporous silica materials are having an impact in traditional pharmaceutical applications and nanomedicine. As excipients, they are allowing the enhancement of poorly soluble drugs with significant improvements in solubility for a large variety of type II drug compounds. Synthetic and structural versatility allows to truly design both mesopore structure and mesopore size with great precision promising to allow for a library of standard materials that can deliver tailored pharmacokinetic release profiles. In this chapter, we highlight some of the important developments in the field of mesoporous materials focusing on early synthetic aspects as well as later functionalisation strategies. The characterisation methods that are employed commonly and may be used to facilitate production and quality assessment are also discussed. Finally, we update the reader with some brief examples of how these non-toxic and biocompatible vehicles are entering pharmaceutical applications.

Mucin and lactoperoxidase are both natively present in the human saliva. Mucin provides lubricating and antiadhesive function, while lactoperoxidase has antimicrobial activity. We propose that combined films of the two proteins can be used as a strategy for surface modification in biomedical applications such as implants or biosensors. In order to design and ultilize mixed protein films, it is necessary to understand the variation in adsorption behavior of the proteins onto different surfaces and how it affects their interaction. The quartz crystal microbalance with dissipation (QCM-D) technique has been used to extract information of the adsorption properties of bovine mucin (BSM) and lactoperoxidase (LPO) to gold, silica, and hydrophobized silica surfaces. The information has further been used to retrieve information of the viscoelastic properties of the adsorbed film. The adsorption and compaction of BSM were found to vary depending on the nature of the underlying bare surface, adsorbing as a thick highly hydrated film with loops and tails extending out in the bulk on gold and as a thinner film with much lower adsorbed amount on silica; and on hydrophobic surfaces, BSM adsorbs as a flat and much more compact layer. On gold and silica, the highly hydrated BSM film is cross-linked and compacted by the addition of LPO, whereas the compaction is not as pronounced on the already more compact film formed on hydrophobic surfaces. The adsorption of LPO to bare surfaces also varied depending on the type of surface. The adsorption profile of BSM onto LPO-coated surfaces mimicked the adsorption to the underlying surface, implying little interaction between the LPO and BSM. The interaction between the protein layers was interpreted as a combination of electrostatic and hydrophobic interactions, which was in turn influenced by the interaction of the proteins with the different substrates.

Friction force measurements have been conducted with a colloid probe on mica and silica (both hydrophilic and hydrophobized) after long (24 h) exposure to high-humidity air. Adhesion and friction measurements have also been performed on cellulose substrates. The long exposure to high humidity led to a large hysteresis between loading and unloading in the friction measurements with separation occurring at large negative applied loads. The large hysteresis in the friction-load relationship is attributed to a contact area hysteresis of the capillary condensate which built up during loading and did not evaporate during the unloading regime. The magnitude of the friction force varied dramatically between substrates and was lowest on the mica substrate and highest on the hydrophilic silica substrate, with the hydrophobized silica and cellulose being intermediate. The adhesion due to capillary forces on cellulose was small compared to that on the other substrates, due to the greater roughness of these surfaces.

Adhesion forces between different protein layers adsorbed on different substrates in aqueous media have been measured by means of an atomic force microscope using the colloid probe technique. The effects of the loading force, the salt concentration and pH of the medium, and the electrolyte type on the strength, the pull-off distance, and the separation energy of such adhesion forces have been analyzed in depth. Two very different proteins (bovine serum albumin and apoferritin) and two dissimilar substrates (silica and polystyrene) were used in the experiments. The results clearly point out a very important contribution of the electrostatic interactions in the adhesion between protein layers.

The atomic force microscope, together with the colloid probe technique, has become a very useful instrument to measure interaction forces between two surfaces. Its potential has been exploited in this work to study the interaction between protein (apoferritin) layers adsorbed on silica surfaces and to analyze the effect of the medium conditions (pH, salt concentration, salt type) on such interactions. It has been observed that the interaction at low salt concentrations is dominated by electrical double layer (at large distances) and steric forces (at short distances), the latter being due to compression of the protein layers. The DLVO theory fits these experimental data quite well. However, a non-DLVO repulsive interaction, prior to contact of the protein layers, is observed at high salt concentration above the isoelectric point of the protein. This behavior could be explained if the presence of hydration forces in the system is assumed. The inclusion of a hydration term in the DLVO theory (extended DLVO theory) gives rise to a better agreement between the theoretical fits and the experimental results. These results seem to suggest that the hydration forces play a very important role in the stability of the proteins in the physiological media.

A number of atomic force microscopy cantilevers have been exhaustively calibrated by a number of techniques to obtain both normal and frictional force constants to evaluate the relative accuracy of the different methods. These were of either direct or indirect character-the latter relies on cantilever resonant frequencies. The so-called Sader [Rev. Sci. Instrum. 70, 3967 (1999)] and Cleveland [Rev. Sci. Instrum. 64, 403 (1993)] techniques are compared for the normal force constant calibration and while agreement was good, a systematic difference was observed. For the torsional force constants, all the techniques displayed a certain scatter but the agreement was highly encouraging. By far the simplest technique is that of Sader, and it is suggested in view of this validation that this method should be generally adopted. The issue of the photodetector calibration is also addressed since this is necessary to obtain the cantilever twist from which the torsional force is calculated. Here a technique of obtaining the torsional photodetector sensitivity by combining the direct and indirect methods is proposed. Direct calibration measurements were conducted in liquid as well as air, and a conversion factor was obtained showing that quantitative friction measurements in liquid are equally feasible provided the correct calibration is performed.

Silica is a very interesting system that has been thoroughly studied in the last decades. One of the most outstanding characteristics of silica suspensions is their stability in solutions at high salt concentrations. In addition to that, measurements of direct-interaction forces between silica surfaces, obtained by different authors by means of surface force apparatus or atomic force microscope (AFM), reveal the existence of a strong repulsive interaction at short distances (below 2 nm) that decays exponentially. These results cannot be explained in terms of the classical Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory, which only considers two types of forces: the electrical double-layer repulsion and the London-van der Waals attraction. Although there is a controversy about the origin of the short-range repulsive force, the existence of a structured layer of water molecules at the silica surface is the most accepted explanation for it. The overlap of structured water layers of different surfaces leads to repulsive forces, which are known as hydration forces. This assumption is based on the very hydrophilic nature of silica. Different theories have been developed in order to reproduce the exponentially decaying behavior (as a function of the separation distance) of the hydration forces. Different mechanisms for the formation of the structured water layer around the silica surfaces are considered by each theory. By the aid of an AFM and the colloid probe technique, the interaction forces between silica surfaces have been measured directly at different pH values and salt concentrations. The results confirm the presence of the short-range repulsion at any experimental condition (even at high salt concentration). A comparison between the experimental data and theoretical fits obtained from different theories has been performed in order to elucidate the nature of this non-DLVO repulsive force.

The atomic force microscope (AFM) is designed to provide high-resolution (in the ideal case, atomic) topographical analysis, applicable to both conducting and nonconducting surfaces. The basic imaging principle is very simple: a sample attached to a piezoelectric positioner is rastered beneath a sharp tip attached to a sensitive cantilever spring. Undulations in the surface lead to deflection of the spring, which is monitored optically. Usually, a feedback loop is employed, which holds the spring deflection constant, and the corresponding movement of the piezoelectric positioner thus generates the image. From this it can be seen that the scanning AFM has all the attributes necessary for the determination of surface and adhesion forces; a sensitive spring to determine the force, a piezoelectric crystal to alter the separation of the tip and surface, which if sufficiently well-calibrated also allows the relative separation of the tip and surface to be calculated. One can routinely quantify both the net surface force (and its separation dependence) as the probe approaches the sample, and any adhesion (pull-off) force on retraction. Interactions in relevant or practical systems may be studied, and, in such cases, a distinct advantage of the AFM technique is that a particle of interest can be attached to the end of the cantilever and the interaction with a sample of choice can be studied, a method often referred to as colloid probe microscopy. The AFM, or, more correctly, the scanning probe microscope, can thus be used to measure surface and frictional forces, the two foci of this article. There have been a wealth of force and friction measurements performed between an AFM tip and a surface, and many of the calibration and analysis issues are identical to those necessary for colloid probe work. We emphasize that this article confines itself primarily to elements of colloid probe measurement using the AFM.