The relationship between the diameter of chemically-functionalized multi-walled carbon nanotubes and their organ biodistribution profiles in vivo.

Carbon nanotubes (CNTs) exhibit unique properties which have led to their applications in the biomedical field as novel delivery systems for diagnosis and therapy purposes. We have previously reported that the degree of functionalization of CNTs is a key factor determining their biological behaviour. The present study broadens the spectrum by investigating the impact of the diameter of CNTs using two series of multi-walled CNTs (MWNTs) with distinct differences in their diameters. Both MWNTs were doubly functionalized by 1,3-dipolar cycloaddition and amidation reactions, allowing the appended functional groups to be further conjugated with radionuclide chelating moieties and antibodies or antibody fragments. All constructs possessed comparable degree of functionalization and were characterized by thermogravimetric analysis, transmission electron microscopy, gel electrophoresis and surface plasmon resonance. The MWNT conjugates were radio-labelled with indium-111, which thereby enabled in vivo single photon emission computed tomography/computed tomography (SPECT/CT) imaging and organ biodistribution study using γ-scintigraphy. The narrow MWNTs (average diameter: 9.2 nm) demonstrated enhanced tissue affinity including non-reticular endothelial tissues compared to the wider MWNTs (average diameter: 39.5 nm). The results indicate that the higher aspect ratio of narrow MWNTs may be beneficial for their future biological applications due to higher tissue accumulation.

Graphene-based electroresponsive scaffolds as polymeric implants for on-demand drug delivery.

Stimuli-responsive biomaterials have attracted significant attention in the field of polymeric implants designed as active scaffolds for on-demand drug delivery. Conventional porous scaffolds suffer from drawbacks such as molecular diffusion and material degradation, allowing in most cases only a zero-order drug release profile. The possibility of using external stimulation to trigger drug release is particularly enticing. In this paper, the fabrication of previously unreported graphene hydrogel hybrid electro-active scaffolds capable of controlled small molecule release is presented. Pristine ball-milled graphene sheets are incorporated into a three dimensional macroporous hydrogel matrix to obtain hybrid gels with enhanced mechanical, electrical, and thermal properties. These electroactive scaffolds demonstrate controlled drug release in a pulsatile fashion upon the ON/OFF application of low electrical voltages, at low graphene concentrations (0.2 mg mL(-1) ) and by maintaining their structural integrity. Moreover, the in vivo performance of these electroactive scaffolds to release drug molecules without any "resistive heating" is demonstrated. In this study, an illustration of how the heat dissipating properties of graphene can provide significant and previously unreported advantages in the design of electroresponsive hydrogels, able to maintain optimal functionality by overcoming adverse effects due to unwanted heating, is offered.

Hemotoxicity of carbon nanotubes.

Carbon nanotubes may enter into the bloodstream and interact with blood components indirectly via translocation following unintended exposure or directly after an intended administration for biomedical purposes. Once introduced into systemic circulation, nanotubes will encounter various proteins, biomolecules or cells which have specific roles in the homeostasis of the circulatory system. It is therefore essential to determine whether those interactions will lead to adverse effects or not. Advances in the understanding of how carbon nanotubes interact with blood proteins, the complement system, red blood cells and the hemostatic system are reviewed in this article. While many studies on carbon nanotube health risk assessment and their biomedical applications have appeared in the last few years, reports on the hemocompatibility of these nanomaterials remain surprisingly limited. Yet, defining the hemotoxicological profile is a mandatory step toward the development of clinically-relevant medications or contrast agents based on carbon nanotubes.

Electroresponsive polymer-carbon nanotube hydrogel hybrids for pulsatile drug delivery in vivo.

Drug release triggered by an external non-invasive stimulus is of great interest for the development of new drug delivery systems. The preparation of an electroresponsive multiwalled carbon nanotube/poly(methylacrylic acid) (MWNT/PMAA)-based hybrid material is reported. The hydrogel hybrids achieve a controlled drug release upon the ON/OFF application of an electric field, giving rise to in vitro and in vivo pulsatile release profiles.

Degree of chemical functionalization of carbon nanotubes determines tissue distribution and excretion profile.

Getting rid of the tubes: An assessment of the retention of functionalized multi-walled carbon nanotubes (MWNTs) in the organs of mice was carried out using single photon emission computed tomography and quantitative scintigraphy (see scheme). Increasing the degree of functionalization on MWNTs enhanced renal clearance, while lower functionalization promoted reticuloendethelial system accumulation.

Insights into the functional roles of alpha(1)-adrenoceptor subtypes in mouse carotid arteries using knockout mice.

1. alpha(1)-Adrenoceptor (AR) subtypes in mouse carotid arteries were characterised using a combination of agonist/antagonist pharmacology and knockout (KO) mice. 2. Phenylephrine (PE) was most potent in the alpha(1B)-KO (pEC(50)=6.9+/-0.2) followed by control (pEC(50)=6.3+/-0.06) and alpha(1D)-KO (pEC(50)=5.5+/-0.07). Both N-[5-(4,5-dihydro-1H-imidazol-2yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulphonamide hydrobromide (A-61603) and 5-hydroxytryptamine (5-HT) were more potent in the alpha(1D)-KO (pEC(50)=7.4+/-0.27 and 7.4+/-0.05, respectively) than the control (pEC(50)=6.9+/-0.09 and 6.9+/-0.08, respectively) and equipotent with the control in the alpha(1B)-KO (pEC(50)=6.7+/-0.07 and 6.8+/-0.04). Maximum responses to PE and A-61603 were reduced in the alpha(1D)-KO compared to control; there was no difference in maximum responses to 5-HT. 3. In control arteries, prazosin and 5-methylurapidil acted competitively with pA(2) of 9.6 and 7.5, respectively. BMY7378 produced antagonism only at the highest concentration used (100 nM; pK(B) 8.3). 4. Prazosin, 5-methylurapidil and BMY7378 acted competitively in alpha(1B)-KO carotid arteries with pA(2) of 10.3, 7.6 and 9.6, respectively. 5. In the alpha(1D)-KO, against PE, 5-methylurapidil produced a pA(2) of 8.1. pK(B) values were calculated for prazosin (10.6) and BMY7378 (7.0). Against A-61603, 5-methylurapidil had a pA(2) of 8.5, prazosin 8.6, while BMY7378 had no effect. 6. In conclusion, the alpha(1B)-KO mediates contraction solely through alpha(1D)-ARs and the alpha(1D)-KO through alpha(1A)-ARs. Extrapolating back to the control from the knockout data suggests that all three subtypes could be involved in the responses, but we propose that the alpha(1D)-AR causes the contractile response and that the role of the alpha(1B)-AR is mainly regulatory.