Activated Carbon/Pectin Composite Enterosorbent for Human Protection from Intoxication with Xenobiotics Pb(II) and Sodium Diclofenac.

The use of enterosorbents-materials which can be administered orally and eliminate toxic substances from the gastrointestinal tract (GIT) by sorption-offers an attractive complementary protection of humans against acute and chronic poisoning. In this study, we report the results of developing a microgranulated binary biomedical preparation for oral use. It was designed with a core-shell structure based on pectin with low degree of esterification as the core, and nanoporous activated carbon produced from rice husk, AC-RH, as the shell, designated as AC-RH@pectin. The adsorption properties of the synthesized materials were studied in aqueous solutions for the removal of lead (II) nitrate as a representative of toxic polyvalent metals and sodium diclofenac as an example of a medicinal drug. The composite enterosorbent demonstrated high adsorption capacity for both adsorbates studied. Adsorption kinetics of lead and diclofenac adsorption by AC-RH, pectin, and AC-RH@pectin, fitted well a pseudo-second-order model. According to the Langmuir adsorption isotherm model, the best fitted isotherm model, the maximum adsorption capacity, qmax, of AC-RH@pectin for diclofenac and for lead (II) was 130.9 mg/g and 227.8 mg/g, respectively. Although qmax of AC-RH for diclofenac, 537.6 mg/g, and qmax of pectin for lead (II), 245.7 mg/g, were higher, the maximum adsorption capacity of AC-RH for lead (II), 52.7 mg/g, was much lower than that of the composite AC-RH@pectin and the adsorption capacity of pectin for diclofenac was negligible. Therefore, the composite material AC-RH@pectin demonstrated substantial efficiency of removing both species which potentially defines it as a more universal enterosorbent suitable for treating poisoning caused by substances of different chemical nature.

Synthetic Amphoteric Cryogels as an Antidote against Acute Heavy Metal Poisoning.

The effectiveness of an amphoteric cryogel (AAC) as an oral sorbent (enerosorbent) for the treatment of acute poisoning of small animals (rats) with heavy metals (HMs) was studied in in vivo experiments. The morphological structure of the cryogel was examined using scanning electron microscopy/energy-dispersive X-ray analysis and confocal microscopy. The use of the cryogel in the treatment of rats administered an LD50 dose of Cd(NO3)2, CsNO3, Sr(NO3)2, or HgCl2 in aqueous solution showed their high survival rate compared to the control group, which did not receive such treatment. The histological and chemical analysis of internal tissues and the biochemical analysis of the blood of the experimental animals showed the effectiveness of the cryogel in protecting the animals against the damaging effect of HMs on the organism comparable with unithiol, a chelating agent based on 2,3-dimercapto-1-propane sulfonic acid sodium salt (DMPS) approved for the treatment of acute poisoning with some heavy metals.

Surface-Functionalized Conducting Nanofibers for Electrically Stimulated Neural Cell Function.

Strategies involving the inclusion of cell-instructive chemical and topographical cues to smart biomaterials in combination with a suitable physical stimulus may be beneficial to enhance nerve-regeneration rate. In this regard, we investigated the surface functionalization of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV)-based electroconductive electrospun nanofibers coupled with externally applied electrical stimulus for accelerated neuronal growth potential. In addition, the voltage-dependent conductive mechanism of the nanofibers was studied in depth to interlink intrinsic conductive properties with electrically stimulated neuronal expressions. Surface functionalization was accomplished using 3-aminopropyltriethoxysilane (APTES) and 1,6-hexanediamine (HDA) as an alternative to costly biomolecule coating (e.g., collagen) for cell adhesion. The nanofibers were uniform, porous, electrically conductive, mechanically strong, and stable under physiological conditions. Surface amination boosted biocompatibility, 3T3 cell adhesion, and spreading, while the neuronal model rat PC12 cell line showed better differentiation on surface-functionalized mats compared to nonfunctionalized mats. When coupled with electrical stimulation (ES), these mats showed comparable or faster neurite formation and elongation than the collagen-coated mats with no-ES conditions. The findings indicate that surface amination in combination with ES may provide an improved strategy to faster nerve regeneration using MEH-PPV-based neural scaffolds.

Nanosized copper(ii) oxide/silica for catalytic generation of nitric oxide from S-nitrosothiols.

Nitric oxide NO, mediates inflammatory and thrombotic processes and designing biomaterials capable of releasing NO in contact with biological tissues is considered to be a major factor aimed at improving their bio- and haemocompatibility and antibacterial properties. Their NO-releasing capacity however is limited by the amount of the NO-containing substance incorporated in the bulk or immobilised on the surface of a biomaterial. An alternative approach is based on the design of a material generating nitric oxide from endogenous NO bearing metabolites by their catalytic decomposition. It offers, at least in theory, an unlimited source of NO for as long as the material remains in contact with blood and the catalyst maintains its activity. In this paper we studied the catalytic properties of novel nanostructured CuO/SiO2 catalysts in generating NO by decomposition of S-nitrosoglutathione (GSNO) in vitro. CuO/SiO2 catalysts with different CuO loadings were synthesized by chemisorption of copper(ii) acetylacetonate on fumed nanosilica followed by calcination. CuO content was controlled by a number of chemisorption-calcination cycles. Fourier-transform infrared spectroscopy and thermogravimetric analysis confirmed the formation of CuO/SiO2 nanoparticles (NPs) with particle size of CuO phase in the range from 71 to 88 nm. Scanning electron microscopy images revealed a uniform distribution of NPs without their sintering or agglomeration. All the materials of the CuO/SiO2 NP series exhibited NO-generating activity from GSNO confirmed by the Griess assay and by measuring the concentration of nitrite and nitrate anions in model solutions such as phosphate buffered saline and bovine serum. This activity is dependent on the material specific surface area and CuO exposure on the surface rather than CuO bulk content. The rate of NO production increased at higher initial concentration of the NO-bearing substrate studied in the range between 0.01 mM and 1.0 mM RSNO, which covers its physiological level. CuO/SiO2 NPs can be used to design polymers with NO generating properties at blood-biomaterial interface which are expected to have improved biocompatibility thus enhancing their potential for medical applications such as surgical tubing, peripheral venous catheters, auxiliary blood circulation devices and drug-eluting balloons.

Correction to: a new Rhodococcus aetherivorans strain isolated from lubricant-contaminated soil as a prospective phenol-biodegrading agent.

The published online version contains mistake in Table 3.

A new Rhodococcus aetherivorans strain isolated from lubricant-contaminated soil as a prospective phenol-biodegrading agent.

Microbe-based decontamination of phenol-polluted environments has significant advantages over physical and chemical approaches by being relatively cheaper and ensuring complete phenol degradation. There is a need to search for commercially prospective bacterial strains that are resistant to phenol and other co-pollutants, e.g. oil hydrocarbons, in contaminated environments, and able to carry out efficient phenol biodegradation at a variable range of concentrations. This research characterizes the phenol-biodegrading ability of a new actinobacteria strain isolated from a lubricant-contaminated soil environment. Phenotypic and phylogenetic analyses showed that the novel strain UCM Ac-603 belonged to the species Rhodococcus aetherivorans, and phenol degrading ability was quantitatively characterized for the first time. R. aetherivorans UCM Ac-603 tolerated and assimilated phenol (100% of supplied concentration) and various hydrocarbons (56.2-94.4%) as sole carbon sources. Additional nutrient supplementation was not required for degradation and this organism could grow at a phenol concentration of 500 mg L-1 without inhibition. Complete phenol assimilation occurred after 4 days at an initial concentration of 1750 mg L-1 for freely-suspended cells and at 2000 mg L-1 for vermiculite-immobilized cells: 99.9% assimilation of phenol was possible from a total concentration of 3000 mg L-1 supplied at daily fractional phenol additions of 750 mg L-1 over 4 days. In terms of phenol degradation rates, R. aetherivorans UCM Ac-602 showed efficient phenol degradation over a wide range of initial concentrations with the rates (e.g. 35.7 mg L-1 h-1 at 500 mg L-1 phenol, and 18.2 mg L-1 h-1 at 1750 mg L-1 phenol) significantly exceeding (1.2-5 times) reported data for almost all other phenol-assimilating bacteria. Such efficient phenol degradation ability compared to currently known strains and other beneficial characteristics of R. aetherivorans UCM Ac-602 suggest it is a promising candidate for bioremediation of phenol-contaminated environments.

Novel nanostructured iron oxide cryogels for arsenic (As(III)) removal.

Novel macroporous iron oxide nanocomposite cryogels were synthesized and assessed as arsenite (As(III)) adsorbents. The two-step synthesis method, by which a porous nanonetwork of iron oxide is firstly formed, allowed a homogeneous dispersion of the iron oxide in the cryogel reaction mixture, regardless of the nature of the co-polymer forming the cryogel structure. The cryogels showed excellent mechanical properties, especially the acrylamide-based cryogel. This gel showed the highest As(III) adsorption capacity, with the maximum value estimated at 118 mg/g using the Langmuir model. The immobilization of the nanostructured iron oxide gel into the cryogel matrix resulted in slower adsorption kinetics, however the cryogels offer the advantage of a stable three-dimensional structure that impedes the release of the iron oxide nanoparticles into the treated effluent. A preliminary toxicity evaluation of the cryogels did not indicate any apparent inhibition of human hepatic cells activity, which together with their mechanical stability and high adsorption capacity for As(III) make them excellent materials for the development of nanoparticle based adsorption devices for drinking water treatment.

Composite Cryogel with Polyelectrolyte Complexes for Growth Factor Delivery.

Macroporous scaffolds composed of chitosan (CHI), hydroxyapatite (HA), heparin (Hep), and polyvinyl alcohol (PVA) were prepared with a glutaraldehyde (GA) cross-linker by cryogelation. Addition of PVA to the reaction mixture slowed down the formation of a polyelectrolyte complex (PEC) between CHI and Hep, which allowed more thorough mixing, and resulted in the development of the homogeneous matrix structure. Freezing of the CHI-HA-GA and PVA-Hep-GA mixture led to the formation of a non-stoichiometric PEC between oppositely charged groups of CHI and Hep, which caused further efficient immobilization of bone morphogenic protein 2 (BMP-2) possible due to electrostatic interactions. It was shown that the obtained cryogel matrix released BMP-2 and supported the differentiation of rat bone marrow mesenchymal stem cells (rat BMSCs) into the osteogenic lineage. Rat BMSCs attached to cryogel loaded with BMP-2 and expressed osteocalcin in vitro. Obtained composite cryogel with PEC may have high potential for bone regeneration and tissue engineering applications.

Investigation of the adsorption capacity of the enterosorbent Enterosgel for a range of bacterial toxins, bile acids and pharmaceutical drugs.

Oral intestinal adsorbents (enterosorbents) are orally administered materials which pass through the gut where they bind (adsorb) various substances. The enterosorbent Enterosgel (Polymethylsiloxane polyhdrate) is recommended as a symptomatic treatment for acute diarrhoea and chronic diarrhoea associated with irritable bowel syndrome (IBS). Since 1980's there have been many Enterosgel clinical trials, however, the detailed mechanism of Enterosgel action towards specific toxins and interaction with concomitantly administered medications has not been fully investigated. Our in vitro study assessed the adsorption capacity of Enterosgel for bacterial enterotoxins and endotoxin, bile acids and interaction with the pharmaceutical drugs; Cetirizine and Amitriptyline hydrochloride. Our data demonstrate the good adsorption capacity of Enterosgel for bacterial toxins associated with gastrointestinal infection, with a lower than the comparator charcoal Charcodote capacity for bile acids whose levels can be raised in IBS patients. Adsorption capacity for the two drugs varied but was significantly lower than Charcodote. These findings suggest that the mechanism of Enterosgel action in the treatment of gastrointestinal infection or IBS is adsorption of target molecules followed by removal from the body. This therapy offers a drug free approach to prevention and treatment of infectious and chronic non-infectious diseases, where intestinal flora and endotoxemia play a role.

Impact of electromagnetic fields on in vitro toxicity of silver and graphene nanoparticles.

The correlation between shape and concentration of silver nanoparticles (AgNPs), their cytotoxicity and formation of reactive oxygen species (ROS) in the presence of electromagnetic fields (EMFs) has been investigated. In addition, the bio-effects caused by the combination of EMFs and graphene nanoparticles (GrNPs) have been also assessed. The AgNPs of three shapes (triangular, spherical and colloidal) and GrNPs were added in high concentrations to the culture of human fibroblasts and exposed to EMF of three different frequencies: 900, 2400 and 7500 MHz. The results demonstrated the dependence of the EMF-induced cytotoxicity on the shape and concentration of AgNPs. The maximal cell killing effect was observed at 900 MHz frequency for NPs of all shapes and concentrations. The highest temperature elevation was observed for GrNPs solution irradiated by EMF of 900 MHz frequency. The exposure to EMF led to significant increase of ROS formation in triangular and colloidal AgNPs solutions. However, no impact of EMF on ROS production was detected for spherical AgNPs. GrNPs demonstrated ROS-protective activity that was dependent on their concentration. Our findings indicate the feasibility to control cytotoxicity of AgNPs by means of EMFs. The effect EMF on the biological activity of AgNPs and GrNPs is reported here for the first time.

MXene Sorbents for Removal of Urea from Dialysate: A Step toward the Wearable Artificial Kidney.

The wearable artificial kidney can deliver continuous ambulatory dialysis for more than 3 million patients with end-stage renal disease. However, the efficient removal of urea is a key challenge in miniaturizing the device and making it light and small enough for practical use. Here, we show that two-dimensional titanium carbide (MXene) with the composition of Ti3C2T x, where T x represents surface termination groups such as -OH, -O-, and -F, can adsorb urea, reaching 99% removal efficiency from aqueous solution and 94% from dialysate at the initial urea concentration of 30 mg/dL, with the maximum urea adsorption capacity of 10.4 mg/g at room temperature. When tested at 37 °C, we achieved a 2-fold increase in urea removal efficiency from dialysate, with the maximum urea adsorption capacity of 21.7 mg/g. Ti3C2T x showed good hemocompatibility; it did not induce cell apoptosis or reduce the metabolizing cell fraction, indicating no impact on cell viability at concentrations of up to 200 µg/mL. The biocompatibility of Ti3C2T x and its selectivity for urea adsorption from dialysate open a new opportunity in designing a miniaturized dialysate regeneration system for a wearable artificial kidney.

Electrically conductive MEH-PPV:PCL electrospun nanofibres for electrical stimulation of rat PC12 pheochromocytoma cells.

The purpose of this study was to prepare an electrically conducting poly[2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) based nanofibrous scaffold and to investigate the synergetic effect of nanofibre structure and electrical stimulation on neuronal growth for possible use in nerve repair. Nanofibres were produced by electrospinning of blended MEH-PPV with polycaprolactone (PCL) at a ratio of 20 : 80, 40 : 60, 50 : 50 and 60 : 40 (v/v). A better electrical conductivity was achieved by using core-sheath structured nanofibres of PCL (core) and MEH-PPV (sheath) produced using the coaxial electrospinning technique. The highest electrical conductivity was observed in the core-sheath nanofibres, while it increased with increasing concentration of MEH-PPV for the blended electrospun nanofibres. The biocompatibility of the electrospun nanofibres was confirmed by MTS and live-dead staining assays using 3T3 fibroblasts and a neuronal rat pheochromocytoma (PC12) cell line. Beta (III) tubulin immunochemistry showed that PC12 cells differentiated into sympathetic neurons on these porous and stiffer electrospun nanofibres coated with collagen I. Improved cell morphology and attachment on the collagen I coated electrospun meshes has been confirmed by SEM analysis. Significant enhancement in neurite formation and neurite outgrowth of PC12 cells on the conductive scaffolds under electrical potential of 500 mV cm-1 for 2 h day-1 suggests the potential use of these scaffolds for nerve repair.

Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.

Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established. In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device. We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood. In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model. This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.

Investigation of rice husk derived activated carbon for removal of nitrate contamination from water.

Development of porous carbons with high specific surface area (>1200mg-1) targeted at nitrate removal from aqueous solutions is investigated by chemical activation of carbonized rice husk. Potassium carbonate is used as activating and desilicating agent. The effect of post-synthetic treatment by gas phase ammoxidation with ozone/ammonia or oxidation with concentrated nitric acid followed by nitrification with urea on main physicochemical properties and on the effectiveness of the activated carbons in nitrate removal is compared with those determined for a pristine activated carbonized rice husk sample. The two-fold enhancement of nitrate removal by the urea-modified activated carbon in comparison with pristine and ammoxidated sample is in direct correlation with the development of surface basic groups.

Amine-Functionalized Electrically Conductive Core-Sheath MEH-PPV:PCL Electrospun Nanofibers for Enhanced Cell-Biomaterial Interactions.

In the present study, a conducting polymer, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) along with a biodegradable polymer poly(ε-caprolactone) (PCL) was used to prepare an electrically conductive, biocompatible, bioactive, and biodegradable nanofibrous scaffold for possible use in neural tissue engineering applications. Core-sheath electrospun nanofibers of PCL as the core and MEH-PPV as the sheath, were surface-functionalized with (3-aminopropyl) triethoxysilane (APTES) and 1,6-hexanediamine to obtain amine-functionalized surface to facilitate cell-biomaterial interactions with the aim of replacing the costly biomolecules such as collagen, fibronectin, laminin, and arginyl-glycyl-aspartic acid (RGD) peptide for surface modification. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the formation of core-sheath morphology of the electrospun nanofibers, whereas Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) revealed successful incorporation of amine functionality after surface functionalization. Adhesion, spreading, and proliferation of 3T3 fibroblasts were enhanced on the surface-functionalized electrospun meshes, whereas the neuronal model rat pheochromocytoma 12 (PC12) cells also adhered and differentiated into sympathetic neurons on these meshes. Under a constant electric field of 500 mV for 2 h/day for 3 consecutive days, the PC12 cells displayed remarkable improvement in the neurite formation and outgrowth on the surface-functionalized meshes that was comparable to those on the collagen-coated meshes under no electrical signal. Electrical stimulation studies further demonstrated that electrically stimulated PC12 cells cultured on collagen I coated meshes yielded more and longer neurites than those of the unstimulated cells on the same scaffolds. The enhanced neurite growth and differentiation suggest the potential use of these scaffolds for neural tissue engineering applications.

Graphene-Based Materials for the Fast Removal of Cytokines from Blood Plasma.

There is a range of medical conditions, which include acute organ failure, bacterial and viral infection, and sepsis, that result in overactivation of the inflammatory response of the organism and release of proinflammatory cytokines into the bloodstream. Fast removal of these cytokines from blood circulation could offer a potentially efficient treatment of such conditions. This study aims at the development and assessment of novel biocompatible graphene-based adsorbents for blood purification from proinflammatory cytokines. These graphene-based materials were chosen on the basis of their surface accessibility for small molecules further facilitated by the interlayer porosity, which is comparable to the size of the cytokine molecules to be adsorbed. Our preliminary results show that graphene nanoplatelets (GnP) exhibit high adsorption capacity, but they cannot be used in direct contact with blood due to the risk of small carbon particle release into the bloodstream. Granulation of GnP using poly(tetrafluoroethylene) as a binder eliminated an undesirable nanoparticle release without affecting the GnP surface accessibility for the cytokine molecules. The efficiency of proinflammatory cytokine removal was shown using a specially designed flow-through system. So far, GnP proved to be among the fastest acting and most efficient sorbents for cytokine removal identified to date, outperforming porous activated carbons and porous polymers.

Preparation of liposomes containing small gold nanoparticles using electrostatic interactions.

The development of liposome-nanoparticle colloid systems offers a versatile approach towards the manufacture of multifunctional therapeutic platforms. A strategy to encapsulate small metallic nanoparticles (<4nm) within multilamellar vesicles, effected by exploiting electrostatic interactions was investigated. Two liposome-gold nanoparticle (lipo-GNP) systems were prepared by the reverse-phase evaporation method employing cationic or anionic surface functionalised particles in combination with oppositely charged lipid compositions with subsequent post-formulation PEGylation. Structural characterisation using electron microscopy and elemental analysis revealed a regular distribution of GNPs between adjacent lipid bilayers of intact liposomes. Nanoparticle encapsulation efficacy of the two lipo-GNP systems was revealed to be significantly different (p=0.03), evaluated by comparing the ratio of measured lipid to gold concentration (loading content) determined by a colorimetric assay and atomic emission spectroscopy, respectively. It was concluded that the developed synthetic strategy is an effective approach for the preparation of liposome-nanoparticle colloids with potential to control the relative concentration of encapsulated particles to lipids by providing favourable electrostatic interactions.

A haemocompatible and scalable nanoporous adsorbent monolith synthesised using a novel lignin binder route to augment the adsorption of poorly removed uraemic toxins in haemodialysis.

Nanoporous adsorbents are promising materials to augment the efficacy of haemodialysis for the treatment of end stage renal disease where mortality rates remain unacceptably high despite improvements in membrane technology. Complications are linked in part to inefficient removal of protein bound and high molecular weight uraemic toxins including key marker molecules albumin bound indoxyl sulphate (IS) and p-cresyl sulphate (PCS) and large inflammatory cytokines such as IL-6. The following study describes the assessment of a nanoporous activated carbon monolith produced using a novel binder synthesis route for scale up as an in line device to augment haemodialysis through adsorption of these toxins. Small and large monoliths were synthesised using an optimised ratio of lignin binder to porous resin of 1 in 4. Small monoliths showing combined significant IS, p-CS and IL-6 adsorption were used to measure haemocompatibility in an ex vivo healthy donor blood perfusion model, assessing coagulation, platelet, granulocyte, T cells and complement activation, haemolysis, adsorption of electrolytes and plasma proteins. The small monoliths were tested in a naive rat model and showed stable blood gas values, blood pressure, blood biochemistry and the absence of coagulopathies. These monoliths were scaled up to a clinically relevant size and were able to maintain adsorption of protein bound uraemic toxins IS, PCS and high molecular weight cytokines TNF-α and IL-6 over 240 min using a flow rate of 300 ml min-1 without platelet activation. The nanoporous monoliths where haemocompatible and retained adsorptive efficacy on scale up with negligible pressure drop across the system indicating potential for use as an in-line device to improve haemodialysis efficacy by adsorption of otherwise poorly removed uraemic toxins.

Properties of Water Bound in Hydrogels.

In this review, the importance of water in hydrogel (HG) properties and structure is analyzed. A variety of methods such as ¹H NMR (nuclear magnetic resonance), DSC (differential scanning calorimetry), XRD (X-ray powder diffraction), dielectric relaxation spectroscopy, thermally stimulated depolarization current, quasi-elastic neutron scattering, rheometry, diffusion, adsorption, infrared spectroscopy are used to study water in HG. The state of HG water is rather non-uniform. According to thermodynamic features of water in HG, some of it is non-freezing and strongly bound, another fraction is freezing and weakly bound, and the third fraction is non-bound, free water freezing at 0 °C. According to structural features of water in HG, it can be divided into two fractions with strongly associated and weakly associated waters. The properties of the water in HG depend also on the amounts and types of solutes, pH, salinity, structural features of HG functionalities.

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.