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[Display omitted] • Traversal dynamics of RBC-NP composite supercarrier with tunable properties are investigated. • Detachment of NPs from RBC occurs in a shear-dependent manner. • Optimal adhesion strength for the release of rigid spherical NPs in microcapillaries is proposed. • Stiffness and shape of NPs alter its detachment effciency. Red blood cell (RBC) membrane-hitchhiking nanoparticles (NPs) have been an increasingly popular supercarrier for targeted drug delivery. However, the kinetic details of the shear-induced NP detachment process from RBC in blood flow remain unclear. Here, we perform detailed computational simulations of the traversal dynamics of an RBC-NP composite supercarrier with tunable properties. We show that the detachment of NPs from RBC occurs in a shear-dependent manner which is consistent with previous experiment results. We quantify the NP detachment rate in the microcapillary flow, and our simulation results suggest that there may be an optimal adhesion strength span of 25–40 μJ/m2 for rigid spherical NPs to improve the supercarrier performance and targeting efficiency. In addition, we find that the stiffness and the shape of NPs alter the detachment efficiency by changing the RBC-NP contact areas. Together, these findings provide unique insights into the shear-dependent NP release from the RBC surface, facilitating the clinical utility of RBC-NP composite supercarriers in targeted and localized drug delivery with high precision and efficiency. [ABSTRACT FROM AUTHOR]

[Display omitted] • Platelet margination and adhesion are two critical events during thrombus formation. • Margination and adhesion dynamics of platelets in microvascular blood flow are investigated. • Platelet margination and adhesion occur in shear-dependent manners. • Adherent platelets have negative impacts on margination dynamics of circulating ones. Platelet margination and adhesion are two critical and closely related steps in thrombus formation. Using dissipative particle dynamics (DPD) method that seamlessly models blood cells, blood plasma, and vessel walls with functionalized surfaces, we quantify the shear-induced margination and adhesion of platelets in microvascular blood flow. The results show that the occurrence of shear-induced RBC-platelet collisions has a remarkable influence on the degree of platelet margination. We characterize the lateral motion of individual platelets by a mean square displacement analysis of platelet trajectories, and find that the wall-induced lift force and the shear-induced displacement in wall-bounded flow cause the variation in near-wall platelet distribution. We then investigate the platelet adhesive dynamics under different flow conditions, by conducting DPD simulations of blood flow in a microtube with fibrinogen-coated wall surfaces. We find that the platelet adhesion is enhanced with the increase of fibrinogen concentration level but decreased with the increase of shear rate. These results are consistent with available experimental results. In addition, we demonstrate that the adherent platelets have a negative impact on the margination dynamics of the circulating platelets, which is mainly due to the climbing effect induced by the adherent ones. Taken together, these findings provide useful insights into the platelet margination and adhesion dynamics, which may facilitate the understanding of the predominant processes governing the initial stage of thrombus formation. [ABSTRACT FROM AUTHOR]

Xylitol is a hygroscopic compound known to protect nasal cavity against bacteria. It has also been developed into nasal spray and evaluated as a potential candidate drug for respiratory diseases. Consequently, it is necessary to study its inhalation toxicity. Based on our previous study on its subacute inhalation toxicity, this study aimed to investigate the safety of xylitol inhalation for long-term use. According to the OECD Test Guideline 413, Sprague-Dawley rats were randomly divided into six groups and exposed with different concentrations of xylitol aerosol or air. After exposure for 90-day, the recovery groups were continued to observe for a recovery period of 28-day. No significant changes in body weight were observed between sham and xylitol groups. Several significant differences in hematological, clinical chemistry, bronchoalveolar lavage fluid were observed, which either had no dose-effect relationship for both male and female rats or were restored during the recovery period. Finally, except for high dose group of xylitol, two rats showed a small amount of inflammatory exudate in alveolar and bronchial cavities, which was restored in the recovery period. The rest of rats showed no obvious difference. For the recovery groups, no significant difference was observed between these two groups. In conclusion, the no observable adverse effect level (NOAEL) of xylitol in our subchronic inhalation toxicological experiments was 2.9 mg/L, which indicated that xylitol for rats' long-time inhalation is tolerant and safe. [Display omitted] • Subchronic inhalation toxicity of xylitol was assessed in rats exposed for 90 days. • The NOAEL of xylitol in subchronic inhalation toxicology is 2.9 mg/L. • Xylitol for long-time inhalation is tolerant and safety for rats. [ABSTRACT FROM AUTHOR]