Yuri Lvov

Halloysite clay nanotubes for controlled release of protective agents.

Halloysite aluminosilicate nanotubes with a 15 nm lumen, 50 nm external diameter, and length of 800 +/- 300 nm have been developed as an entrapment system for loading, storage, and controlled release of anticorrosion agents and biocides. Fundamental research to enable the control of release rates from hours to months is being undertaken. By variation of internal fluidic properties, the formation of nanoshells over the nanotubes and by creation of smart caps at the tube ends it is possible to develop further means of controlling the rate of release. Anticorrosive halloysite coatings are in development and a self-healing approach has been developed for repair mechanisms through response activation to external impacts. In this Perspective, applications of halloysite as nanometer-scale containers are discussed, including the use of halloysite tubes as drug releasing agents, as biomimetic reaction vessels, and as additives in biocide and protective coatings. Halloysite nanotubes are available in thousands of tons, and remain sophisticated and novel natural nanomaterials which can be used for the loading of agents for metal and plastic anticorrosion and biocide protection.

Cytocompatibility and Uptake of Halloysite Clay Nanotubes

Halloysite is aluminosilicate clay with hollow tubular structure of 50 nm external diameter and 15 nm diameter lumen. Halloysite biocompatibility study is important for its potential applications in polymer composites, bone implants, controlled drug delivery, and for protective coating (e.g., anticorrosion or antimolding). Halloysite nanotubes were added to different cell cultures for toxicity tests. Its fluorescence functionalization by aminopropyltriethosilane (APTES) and with fluorescently labeled polyelectrolyte layers allowed following halloysite uptake by the cells with confocal laser scanning microscopy (CLSM). Quantitative Trypan blue and MTT measurements performed with two neoplastic cell lines model systems as a function of the nanotubes concentration and incubation time indicate that halloysite exhibits a high level of biocompatibility and very low cytotoxicity, rendering it a good candidate for household materials and medicine. A combination of transmission electron microscopy (TEM), scanning electron microscopy (SEM), and scanning force microscopy (SFM) imaging techniques have been employed to elucidate the structure of halloysite nanotubes.

Proof of multilayer structural organization in self-assembled polycation-polyanion molecular films

Abstract Multilayer organization of ultrathin polycation-polyanion self-assembled films is demonstrated using two approaches. (1) Fabrication of polyion superlattices with alternation of three different polyelectrolytes in (ABCB) n fashion, which gives rise to a Bragg peak in X-ray reflectivity. The spacing d=93.4 A corresponds to the repeat unit (ABCB) n . (2) Drying-induced manipulation of the film surface at regular intervals. Normally the layer-by-layer adsorption is carried out by keeping the film wet throughout all deposition cycles. Alternatively the film surface can be manipulated by gently drying the film in a stream of nitrogen or air after the adsorption of every layer. When the films are dried at regular intervals m during the alternating deposition of a polyanion and a polycation (AB) m (e.g. m =3 for drying after deposition of every 6th layer), up to four orders of Bragg peaks are observed in X-ray reflectivity. In the case of poly(styrenesulphonate) alternated with poly(allylamine) the observed superlattice spacings d m were d 2 =104 A , d 3 =150 A and d 4 =188 A . In both cases the observation of a superlattice structure probably results from the artificially enhanced variation in electron density along the layer normal on a length scale larger than the interfacial width of adjacent layers.

Layer-by-layer self-assembled shells for drug delivery☆

There are several requirements for the safe and effective delivery of therapeutic agents for human use. Direct injection of drugs may cause side effects due to their permeation to other, undiseased regions of the body so that concealment and targeting with appropriate materials is a critical consideration in the design of practical drug delivery systems. In particular, carriers with structures which can be flexibly controlled are more useful since functional structure units can be assembled in component-by-component and/or layer-by-layer fashion. In this review, we focus on preparation of layer-by-layer shells directed at drug delivery applications. After a description of the fundamentals of layer-by-layer (LbL) assembly, recent progress in the field of self-assembled microshells and nanoshells for drug delivery applications are summarized. In addition, concepts developed to solve current difficulties are also described. Encapsulation of insoluble drugs in nanoshells and their delivery can satisfy some of the demands of practical medical use. Thus, aqueous suspensions of insoluble drugs have been subjected to powerful ultrasonic treatment followed by sequential addition of polycations and polyanions to the particle solution leading to assembly of ultra-thin polyelectrolyte shells on the nano-sized drug particles. In another innovative example, stepwise release of drugs from LbL films of mesoporous capsules to the exterior in the absence of external stimuli was demonstrated. It can be regarded as stimuli-free auto-modulated material release.

Biomedical applications of electrostatic layer-by-layer nano-assembly of polymers, enzymes, and nanoparticles.

The introduction of electrostatic layer-by-layer (LbL) self-assembly has shown broad biomedical applications in thin film coating, micropatterning, nanobioreactors, artificial cells, and drug delivery systems. Multiple assembly polyelectrolytes and proteins are based on electrostatic interaction between oppositely charged layers. The film architecture is precisely designed and can be controlled to 1-nm precision with a range from 5 to 1000 nm. Thin films can be deposited on any surface including many widely used biomaterials. Microencapsulation of micro/nanotemplates with multilayers enabled cell surface modification, controlled drug release, hollow shell formation, and nanobioreactors. Both in vitro and in vivo studies indicate potential applications in biology, pharmaceutics, medicine, and other biomedical areas.

New nanocomposite films for biosensors: layer-by-layer adsorbed films of polyelectrolytes, proteins or DNA

Abstract This report describes the construction of ultrathin multicomponent films with an internal structure on the nanometre scale. In the simplest case, the films are built-up by the subsequent adsorption of polyanions and polycations. They can be fabricated on inorganic substrates such as glass, quartz or silicon wafers, or on various organic materials. The polymeric interlayers can incorporate materials with desired electrical or optical properties. The average thickness of the layers can be fine-tuned with Angstrom precision by the addition of suitable salts. They are temperature stable up to at least 200°C and can be laterally structured using conventional photolithographic techniques. The films provide for a well-defined substrate-independent interface for the immobilization of biological macromolecules, such as proteins or DNA, in their active state. The immobilization of streptavidin enables the controlled attachment of any biotinylated molecule with no resulting loss in its biological activity. Area-selective immobilization provides the possibility of built-in quality control for the fabrication of biosensors with separated reference and sample areas on the same substrate.

Layer-by-Layer-Coated Gelatin Nanoparticles as a Vehicle for Delivery of Natural Polyphenols

Natural polyphenols with previously demonstrated anticancer potential, epigallocatechin gallate (EGCG), tannic acid, curcumin, and theaflavin, were encased into gelatin-based 200 nm nanoparticles consisting of a soft gel-like interior with or without a surrounding LbL shell of polyelectrolytes (polystyrene sulfonate/polyallylamine hydrochloride, polyglutamic acid/poly-l-lysine, dextran sulfate/protamine sulfate, carboxymethyl cellulose/gelatin, type A) assembled using the layer-by-layer technique. The characteristics of polyphenol loading and factors affecting their release from the nanocapsules were investigated. Nanoparticle-encapsulated EGCG retained its biological activity and blocked hepatocyte growth factor (HGF)-induced intracellular signaling in the breast cancer cell line MBA-MD-231 as potently as free EGCG.

Selective Modification of Halloysite Lumen with Octadecylphosphonic Acid: New Inorganic Tubular Micelle

Selective fatty acid hydrophobization of the inner surface of tubule halloysite clay is demonstrated. Aqueous phosphonic acid was found to bind to alumina sites at the tube lumen and did not bind the tubes outer siloxane surface. The bonding was characterized with solid-state nuclear magnetic resonance ((29)Si, (13)C, (31)P NMR), Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy. NMR and FTIR spectroscopy of selectively modified tubes proved binding of octadecylphosphonic acid within the halloysite lumen through bidentate and tridentate P-O-Al linkage. Selective modification of the halloysite clay lumen creates an inorganic micelle-like architecture with a hydrophobic aliphatic chain core and a hydrophilic silicate shell. An enhanced capacity for adsorption of the modified halloysite toward hydrophobic derivatives of ferrocene was shown. This demonstrates that the different inner and outer surface chemistry of clay nanotubes can be used for selective modification, enabling different applications from water purification to drug immobilization and controlled release.

Halloysite Tubes as Nanocontainers for Anticorrosion Coating with Benzotriazole

Halloysite clay nanotubes were investigated as a tubular container for the corrosion inhibitor benzotriazole. Halloysite is a naturally occurring cylindrical clay mineral with an internal diameter in the nanometer range and a length up to several micrometers, yielding a high-aspect-ratio hollow tube structure. Halloysite may be used as an additive in paints to produce a functional composite coating material. A maximum benzotriazole loading of 5% by weight was achieved for clay tubes of 50 nm external diameters and lumen of 15 nm. Variable release rates of the corrosion inhibitor were possible in a range between 5 and 100 h, as was demonstrated by formation of stoppers at tube openings. The anticorrosive performance of the sol-gel coating and paint loaded with 2-5% of halloysite-entrapped benzotriazole was tested on copper and on 2024-aluminum alloy by direct exposure of the metal plates to corrosive media. Kinetics of the corrosion spot formation at the coating defects was analyzed by the scanning vibrating electrode technique, and an essential damping of corrosion development was demonstrated for halloysite-loaded samples.

Introduction to nanocoatings produced by layer-by-layer (LbL) self-assembly☆

Studies on the adsorption of oppositely charged colloidal particles ultimately resulted in multilayered polyelectrolyte self-assembly. The inception of layer-by-layer constructed particles facilitated the production of multifunctional, stimuli-responsive carrier systems. An array of synthetic and natural polyelectrolytes, metal oxides and clay nanoparticles is available for the construction of multilayered nanocoats on a multitude of substrates or removable cores. Numerous substrates can be encapsulated utilizing this technique including dyes, enzymes, drugs and cells. Furthermore, the outer surface of the particles presents and ideal platform that can be functionalized with targeting molecules or catalysts. Some processing parameters determining the properties of these successive self-assembly constructs are the surface charge density, coating material concentration, rinsing and drying steps, temperature and ionic strength of the medium. Additionally, the simplicity of the layer-by-layer assembly technique and the availability of established characterization methods, render these constructs extremely versatile in applications of sensing, encapsulation and target- and trigger-responsive drug delivery.