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.
Porosity over a broad range (typically 0.001–300 μm in diameter) of tissue scaffolds provides appropriate conditions for diffusion and adsorption of small molecules and macromolecules, migration of cells through the scaffold, and adequate cell proliferative capacity. Characterisation of pores over this large range poses a problem especially when analysing soft polymer hydrogels, as no one methodology can adequately cover the entire range. This work describes a combined technique used for evaluation of the porous structure of a collagen hydrogel (dermal substitute Integra®) on the basis of NMR-cryoporometry (sensitive to nanopores) and confocal laser scanning microscopy (CLSM) imaging (sensitive to macropores). Thermodesorption of water, diffusion of proteins through a collagen membrane, migration and growth of normal primary human skin fibroblasts, and the interaction kinetics of 3T3 mouse fibroblast cells (using a quartz crystal microbalance) with collagen were analysed with respect to the porous structure of the material. The contribution to the total porosity of pores with a diameter of less than 100 nm is low, at approximately 3–5%, a figure estimated using the methods described above. However, these pores are the main contributor to the specific surface area (S ≈ 120 m2 g−1) as larger diameter macropores, with diameters of 20–200 μm, have a much lower surface area at S ≈ 0.4 m2 g−1 relative to their large pore volume V = 14.4 cm3 g−1
The deployment of a vascular stent during angioplasty has greatly reduced the risks of restenosis. However, the presence of the device still induces a host response as well as a mechanical action on the blood vessel wall and an alteration of the haemodynamics. Platelet and inflammatory cells can adhere on the stent surface and be activated to produce biochemical signals able to stimulate an excessive proliferation of the smooth muscle cells with the consequent obstruction of the vessel lumen. For these reasons, the host response to two of the materials used in stent manufacture, stainless steel and diamond-like carbon, was investigated in vitro. The data showed that stainless steel induced a higher level of host response both in terms of platelet aggregation and macrophage activation. However, the spreading of inflammatory cells was more accentuated on diamond-like carbon. The inflammatory cells produced levels of platelet-derived growth factor, a key signal in smooth muscle cell proliferation, similar to stainless steel thus suggesting that carbon coatings may not be able to prevent restenosis.
Advances in nanotechnology have seen the development of several microbiocidal nanoparticles displaying activity against biofilms. These applications benefit from one or more combinations of the nanoparticle properties. Nanoparticles may indeed concentrate drugs on their surface resulting in polyvalent effects and improved efficacy to fight against bacteria. Nanodiamonds (NDs) are among the most promising new materials for biomedical applications. We elucidate in this paper the effect of menthol modified nanodiamond (ND-menthol) particles on bacterial viability against Grampositive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. We show that while ND-menthol particles are non-toxic to both pathogens, they show significant antibiofilm activity. The presence of ND-menthol particles reduces biofilm formation more efficiently than free menthol, unmodified oxidized NDs and ampicillin, a commonly used antibiotic. Our findings might be thus a step forward towards the development of alternative non antibiotic based strategies targeting bacterial infections.
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