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Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed.

Adsorption of myoglobin (Mb), bovine serum albumin (BSA) and γ-globulin (GG) onto activated carbons (ACs) with different pore size distributions, and poly(vinyl alcohol) (PVA) monolithic cryogels containing AC particles was studied. The highest initial rate of Mb adsorption was observed for AC having the largest specific surface area (1939 m(2) g(-1)) and pore volume (1.82 cm(3) g(-1)). The adsorption kinetics of proteins was characterized by a bimodal shape of the distribution f(D) function of an effective diffusion coefficient. Adsorption isotherms of Mb and GG were of Freundlich type within the studied range of equilibrium concentrations (10-150 μg mL(-1)). The distributions of free energy of protein adsorption were bimodal and reflected both interactions with carbon surfaces and self-association of proteins. Adsorbed amounts of Mb were the highest among the proteins studied (up to 700 mg g(-1) carbon), which was attributed to the higher fraction of pores accessible for Mb. Incorporation of carbon particles into PVA-based cryogel resulted in macroporous monolithic composite materials (AC-PVA) exhibiting good flow-through properties. Scanning electron microscopy of the composites showed macroporous aggregates of carbon particles held together by films and bridges of PVA. The rates of adsorption and adsorbed amounts of proteins on AC-PVA were reduced compared to the pristine carbon and depended on the carbon content in the composites. Nevertheless, adsorption of Mb on AC-PVA took place even in the presence of 500-fold higher concentration of BSA. This indicated a possibility of Mb clearance from blood plasma using the PVA-carbon monoliths.

Quasi-elastic light scattering (QELS) and quartz crystal microbalance (QCM) non-equilibrium and equilibrium studies of competitive interactions of pairs of polymers and proteins with fumed silica and ceramic coatings deposited on QCM crystals show complex interfacial behaviour. The effects observed depend on the adsorption sequence of co-adsorbates, their chemical structure and the morphology and chemical structure of the adsorbent. The equilibrium adsorption and dynamics of interactions of macromolecules with bare adsorbent surface and surface covered with pre-adsorbed polymer or protein, are compared in terms of the distribution functions of the Gibbs free energy of adsorption, which varied from -25 kJ mol(-1) on a bare surface to almost 0 kJ mol(-1) on a polymer or protein coated surface.

Boronate-containing thin polyacrylamide gels (B-Gel), polymer brushes (B-Brush) and chemisorbed organosilane layers (B-COSL) were prepared on the surface of glass slides and studied as substrates for carbohydrate-mediated cell adhesion. B-COSL- and B-Brush-modified glass samples exhibited multiple submicron structures densely and irregularly distributed on the glass surface, as found by scanning electron microscopy and atomic force microscopy. B-Gel was ca. 0.1 mm thick and contained pores with effective size of 1-2 microm in the middle and of 5-20 microm on the edges of the gel sample as found by confocal laser scanning microscopy. Evidence for the presence of phenylboronic acid in the samples was given by time-of-flight secondary ion mass-spectrometry (ToF SIMS), contact angle measurements performed in the presence of fructose, and staining with Alizarin Red S dye capable of formation specific, fluorescent complexes with boronic acids. A comparative study of adhesion and cultivation of animal cells on the above substrates was carried out using murine hybridoma M2139 cell line as a model. M2139 cells adhered to the substrates in the culture medium without glucose or sodium pyruvate at pH 8.0, and then were cultivated in the same medium at pH 7.2 for 4 days. It was found that the substrates of B-Brush type were superior both regarding cell adhesion and viability of the adhered cells, among the substrates studied. MTT assay confirmed proliferation of M2139 cells on B-Brush substrates. Some cell adhesion was also registered in the macropores of B-Gel substrate. The effects of surface microstructure of the boronate-containing polymers on cell adhesion are discussed. Transparent glass substrates grafted with boronate-containing copolymers offer good prospects for cell adhesion studies and development of cell-based assays.

Degradation of a commercially available collagen-glycosaminoglycan dermal equivalent matrix was studied using electrochemical techniques. Degradation was accelerated by exposure to gamma radiation followed by storage at elevated temperatures or exposure to enzymes. The time-dependent diffusion of a small, electrochemically active, molecular probe, potassium ferrocyanide, through the matrix was monitored via changes in the oxidation peak currents of cyclic voltammograms. These measurements were made using a two-compartment diffusion chamber with the sample positioned well away from the working electrodes and a single-compartment electrode cell where the matrix was in direct contact with the working electrode. The relative merits of these two approaches are considered. Regardless of the approach chosen, amperometry appears well suited to monitoring progressive diffusivity changes through mechanically weak porous structures subject to different solution environments.

Radical copolymerization of acrylamide (Am) (90 mol%) with N-acryloyl-m-aminophenylboronic acid (NAAPBA) (10 mol%) carried out on the surface of glass slides in aqueous solution and in the absence of chemical cross-linkers, resulted in the formation of thin semitransparent gels. The phenylboronic acid (PBA) ligand density was ca. 160 micromol/ml gel. The gels exhibited a macroporous structure and displayed optical response to sucrose, lactose, glucose and fructose in 50 mM sodium phosphate buffer, in the pH range from 6.5 to 7.5. The response was fairly reversible and linearly depended on glucose concentration in the wide concentration range from 1 to 60 mM at pH 7.3. The character of response was explained by the balance of two competing equilibrium processes: binding of glucose to phenylboronate anions and binary hydrophobic interactions of neutral PBA groups. The apparent diffusion coefficient of glucose in the gels was ca. 2.5 x 10(-7) cm(2)/s. A freshly prepared gel can be used daily for at least 1 month without changes in sensitivity. Autoclaving (121 degrees C, 1.2 bar, 10 min) allows for the gels sterilization, which is important for their use as glucose sensors in fermentation processes., (2008 John Wiley & Sons, Ltd.)

The nanoporous structure of collagen-glycosaminoglycan (CG) hydrogels was studied using 1H NMR spectroscopy and thermally stimulated depolarisation (TSD) current with layer-by-layer freezing-out of bulk and interfacial water. The depression of the freezing point of water is related to the size of the nanopore, to which it is confined. Changes in the Gibbs free energy of the unfrozen interfacial water are related to the amount of bound water in the hydrogel matrix and to the re-arrangement of the 3D network structure of the biopolymer. Analysis of the thermodynamic properties of bulk and interfacial water using the layer-by-layer freezing-out technique combined with NMR and TSDC provides valuable information about the structural features of CG hydrogels that can be used for characterisation of different types of hydrogels and soft tissue scaffolds, artificial skin substitutes and other biomaterials.

In order to study the haemocompatibility of metal and carbon coatings, fibrinogen adsorption and platelet adhesion to various coatings have been investigated. Two metallic coatings--titanium and zirconium, and two carbon coatings - isotropic diamond-like and isotropic graphite-like coatings, were prepared by plasma vapour deposition onto stainless steel substrate. It has been shown that the adsorption of fibrinogen to metal and carbon coatings and its post-adsorptive transition are dependent on both the material properties and the fibrinogen environment. The adsorption of fibrinogen from human plasma on titanium and zirconium coatings is similar to that on uncoated stainless steel surface. Both carbon coatings adsorb much greater amount of fibrinogen from plasma, and fibrinogen retention by carbon surfaces is also greater than by metal surfaces. Increased numbers of adhered platelets have been found on both carbon coatings in comparison to the metal materials, although this does not correlate with the amount of adsorbed fibrinogen.

Structural characteristics of a series of MAST carbons were studied using scanning electron microscopy images and the nitrogen adsorption isotherms analyzed with several models of pores and different adsorption equations. A developed model of pores as a mixture of gaps between spherical nanoparticles and slitlike pores was found appropriate for MAST carbons. Adsorption of ibuprofen [2-(4-isobutylphenyl)propionic acid] on activated carbons possessing different pore size distributions in protein-free and bovine serum albumin (BSA)-containing aqueous solutions reveals the importance of the contribution of mesopores to the total porosity of adsorbents. The influence of the mesoporosity increases when considering the removal of the drug from the protein-containing solution. Cellulose-coated microporous carbon Norit RBX adsorbs significantly smaller amounts of ibuprofen than uncoated micro/mesoporous MAST carbons whose adsorption capability increases with increasing mesoporosity and specific surface area, burnoff dependent variable. A similar effect of broad pores is observed on adsorption of fibrinogen on the same carbons. Analysis of the ibuprofen adsorption data using Langmuir and D'Arcy-Watt equations as the kernel of the Fredholm integral equation shows that the nonuniformity of ibuprofen adsorption complexes diminishes with the presence of BSA. This effect may be explained by a partial adsorption of ibuprofen onto protein molecules immobilized on carbon particles and blocking of a portion of narrow pores.