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Blood is a complex fluid with non-Newtonian characteristics and consists primarily of a concentrated suspension of red blood cells (RBCs) characterized by high deformability and aggregability. The majority of both research and clinical investigations on blood rheology is based on steady shear measurements aimed at determining blood viscosity as a function of shear rate. On the other hand, investigations of blood rheology in the linear viscoelastic regime are sparse in the literature and currently limited. In principle, small amplitude oscillatory flow is best suited to study blood microstructure and rheology under quasi-static conditions, which are relevant in a range of applications, from blood storage to blood aggregability testing. Here, we present the first systematic experimental investigation of blood rheological behavior in the linear viscoelastic regime, by performing oscillatory shear measurements by conventional bulk rheology. The storage (G′) and loss (G″) moduli of whole human blood have been measured over an extended range of frequencies [0.1–30 rad/s]. Data show that G″ predominates over G′ across the entire tested range of frequency. By comparing steady and oscillatory shear viscosity, it was found that the Cox-Merz rule is followed to a good approximation, with higher deviations at small shear rate/frequencies. The effects of RBC volume fraction and of aggregating media (i.e., dextran solution at two different concentrations) have been also investigated. Overall, our results are consistent with the behavior of a weakly attractive suspension, where RBCs form reversible aggregates that can be broken by the action of flow.

Malaria is associated with significant microcirculation disorders, especially when the infection reaches its severe stage. This can lead to a range of fatal conditions, from cerebral malaria to multiple organ failure, of not fully understood pathogenesis. It has recently been proposed that a breakdown of the glycocalyx, the carbohydrate-rich layer lining the vascular endothelium, plays a key role in severe malaria, but direct evidence supporting this hypothesis is still lacking. Here, the interactions betweenPlasmodium falciparuminfected red blood cells (PfRBCs) and endothelial glycocalyx are investigated by developing anin vitro, physiologically relevant model of human microcirculation based on microfluidics. Impairment of the glycocalyx is obtained by enzymatic removal of sialic acid residues, which, due to their terminal location and net negative charge, are implicated in the initial interactions with contacting cells. We show a more than twofold increase ofPfRBC adhesion to endothelial cells upon enzymatic treatment, relative to untreated endothelial cells. As a control, no effect of enzymatic treatment on healthy red blood cell adhesion is found. The increased adhesion ofPfRBCs is also associated with cell flipping and reduced velocity as compared to the untreated endothelium. Altogether, these results provide a compelling evidence of the increased cytoadherence ofPfRBCs to glycocalyx-impaired vascular endothelium, thus supporting the advocated role of glycocalyx disruption in the pathogenesis of this disease.

Interaction of microstructured fluids with skin is ubiquitous in everyday life, from the use of cosmetics, lotions, and drugs, to personal care with detergents or soaps. The formulation of microstructured fluids is crucial for the control of the transdermal transport. In biomedical applications transdermal delivery is an efficient approach, alternative to traditional routes like oral and parenteral administration, for local release of drugs. Poor skin permeability, mainly due to its outer layer, which acts as the first barrier against the entry of external compounds, greatly limits the applicability of transdermal delivery. In this review, we focus on recent studies on the improvement of skin transport efficiency by using microemulsions (ME). Quantitative techniques, which are able to investigate both skin morphology and penetration processes, are also reviewed. ME are increasingly used as transdermal systems due to their low preparation cost, stability and high bioavailability. ME may act as penetration enhancers for many active principles, but ME microstructure should be chosen appropriately considering several factors such as ratio and type of ingredients and physic-chemical properties of the active components. ME microstructure is strongly affected by the flow conditions applied during processing, or during spreading and rubbing onto skin. Although the role played by ME microstructure has been generally recognized, the skin transport mechanisms associated with different ME microstructures are still to be elucidated and further investigations are required to fully exploit the potential of ME in transdermal delivery.