Nano carriers for drug transport across the blood-brain barrier.

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.

Activated carbons and carbon-containing poly(vinyl alcohol) cryogels: characterization, protein adsorption and possibility of myoglobin clearance.

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.

Competitive adsorption of macromolecules and real-time dynamics of Vroman-like effects.

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.

Assessment of tissue scaffold degradation using electrochemical techniques.

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.

Characterisation of the nanoporous structure of collagen-glycosaminoglycan hydrogels by freezing-out of bulk and bound water.

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.

Fibrinogen adsorption and platelet adhesion to metal and carbon coatings.

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.