Use of submicron vaterite particles serves as an effective delivery vehicle to the respiratory portion of the lung

© 2018 Gusliakova, Atochina-Vasserman, Sindeeva, Sindeev, Pinyaev, Pyataev, Revin, Sukhorukov, Gorin and Gow. Nano- and microencapsulation has proven to be a useful technique for the construction of drug delivery vehicles for use in vascular medicine. However, the possibility of using these techniques within the lung as an inhalation delivery mechanism has not been previously considered. A critical element of particle delivery to the lung is the degree of penetrance that can be achieved with respect to the airway tree. In this study we examined the effectiveness of near infrared (NIR) dye (Cy7) labeled calcium carbonate (vaterite) particles of 3.15, 1.35, and 0.65 μm diameter in reaching the respiratory portion of the lung. First of all, it was shown that, interaction vaterite particles and the components of the pulmonary surfactant occurs a very strong retardation of the recrystallization and dissolution of the particles, which can subsequently be used to create systems with a prolonging release of bioactive substances after the particles penetrate the distal sections of the lungs. Submicro- and microparticles, coated with Cy7 labeled albumin as a model compound, were delivered to mouse lungs via tracheostomy with subsequent imaging performed 24, 48, and 72 h after delivery by in vivo fluorescence. 20 min post administration particles of all three sizes were visible in the lung, with the deepest penetrance observed with 0.65 μm particles. In vivo biodistribution was confirmed by fluorescence tomography imaging of excised organs post 72 h. Laser scanning confocal microscopy shows 0.65 μm particles reaching the alveolar space. The delivery of fluorophore to the blood was assessed using Cy7 labeled 0.65 μm particles. Cy7 labeled 0.65 μm particles efficiently delivered fluorescent material to the blood with a peak 3 h after particle administration. The pharmacokinetics of NIR fluorescence dye will be shown. These studies establish that by using 0.65 μm particles loaded with Cy7 we can efficiently access the respiratory portion of the lung, which represents a potentially efficient delivery mechanism for both the lung and the vasculature

CFD and MRI studies of hemodynamic changes after flow diverter implantation in a patient-specific model of the cerebral artery

Abstract: Flow changes after flow diverter (FD) placement may be assessed by 4D phase-contrast MR-angiography (4D flow MRI) or simulated by computational fluid dynamics (CFD). However, cross-validation and future assessments with both approaches to take advantage of their individual strengths are required. In this study, we investigate the influence of a FD on intra-aneurysmal blood flow using both MRI experiments and CFD simulations. MR measurements were performed in a true-to-scale silicone model of a wide-neck saccular aneurysm of the distal internal carotid artery before and after FD deployment. An experimental setup, including a computer-controlled piston pump, was assembled to simulate pulsatile blood flow. For CFD studies, a virtual stenting technique was used to place a FD into the aneurysm model. Boundary conditions were applied according to MRI-measured flow data. A qualitative and quantitative agreement of velocity fields measured by CFD and MRI both before and after FD placement was demonstrated. The intra-aneurysmal flow reduction in the CFD results was 19%, while a reduction of 23% was measured by 4D flow MRI. Despite of the low spatial resolution, MRI was able to correctly determine the flow pattern in the aneurysm. The pre-treatment CFD simulation could be helpful in predicting the outcome of a FD treatment, while a post-interventional MRI could prove the desired treatment effect.Fil: Frolov, S. V.. Tambov State Technical University; RusiaFil: Sindeev, S. V.. Tambov State Technical University; RusiaFil: Kirschke, J. S.. Universitat Technical Zu Munich; AlemaniaFil: Arnold, P.. Universitat Technical Zu Munich; AlemaniaFil: Prothmann, S.. Universitat Technical Zu Munich; AlemaniaFil: Liepsch, D.. Munich University of Applied Sciences; AlemaniaFil: Balasso, A.. Ludwig Maximilians Universitat; AlemaniaFil: Potlov, A.. Tambov State Technical University; RusiaFil: Larrabide, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; ArgentinaFil: Kaczmarz, S.. Universitat Technical Zu Munich; Alemani

Hidden stage of intracranial hemorrhage in newborn rats studied with laser speckle contrast imaging and wavelets

Using the laser speckle contrast imaging and wavelet-based analyses, we investigate a latent (a "hidden") stage of the development of intracranial hemorrhages (ICHs) in newborn rats. We apply two measures based on the continuous wavelet-transform of blood flow velocity in the sagittal sinus, namely, the spectral energy in distinct frequency ranges and a multiscality degree characterizing complexity of experimental data. We show that the wavelet-based multifractal formalism reveals changes in the cerebrovascular blood flow at the development of ICH

Use of submicron vaterite particles serves as an effective delivery vehicle to the respiratory portion of the lung

© 2018 Gusliakova, Atochina-Vasserman, Sindeeva, Sindeev, Pinyaev, Pyataev, Revin, Sukhorukov, Gorin and Gow. Nano- and microencapsulation has proven to be a useful technique for the construction of drug delivery vehicles for use in vascular medicine. However, the possibility of using these techniques within the lung as an inhalation delivery mechanism has not been previously considered. A critical element of particle delivery to the lung is the degree of penetrance that can be achieved with respect to the airway tree. In this study we examined the effectiveness of near infrared (NIR) dye (Cy7) labeled calcium carbonate (vaterite) particles of 3.15, 1.35, and 0.65 μm diameter in reaching the respiratory portion of the lung. First of all, it was shown that, interaction vaterite particles and the components of the pulmonary surfactant occurs a very strong retardation of the recrystallization and dissolution of the particles, which can subsequently be used to create systems with a prolonging release of bioactive substances after the particles penetrate the distal sections of the lungs. Submicro- and microparticles, coated with Cy7 labeled albumin as a model compound, were delivered to mouse lungs via tracheostomy with subsequent imaging performed 24, 48, and 72 h after delivery by in vivo fluorescence. 20 min post administration particles of all three sizes were visible in the lung, with the deepest penetrance observed with 0.65 μm particles. In vivo biodistribution was confirmed by fluorescence tomography imaging of excised organs post 72 h. Laser scanning confocal microscopy shows 0.65 μm particles reaching the alveolar space. The delivery of fluorophore to the blood was assessed using Cy7 labeled 0.65 μm particles. Cy7 labeled 0.65 μm particles efficiently delivered fluorescent material to the blood with a peak 3 h after particle administration. The pharmacokinetics of NIR fluorescence dye will be shown. These studies establish that by using 0.65 μm particles loaded with Cy7 we can efficiently access the respiratory portion of the lung, which represents a potentially efficient delivery mechanism for both the lung and the vasculature

WAVELET-BASED ANALYSIS OF CEREBROVASCULAR DYNAMICS IN NEWBORN RATS WITH INTRACRANIAL HEMORRHAGES

Intracranial hemorrhage (IH) is a major problem of neonatal intensive care. The incidence of IH is typically asymptomatic and cannot be effectively detected by standard diagnostic methods. The mechanisms underlying IH are unknown but there is evidence that stress-induced disorders in adrenergic regulation of cerebral venous blood flow (CVBF) are among the main reasons. Quantitative and qualitative assessment of CVBF could significantly advance understanding of the nature of IH in newborns. In this work, we analyze variations of CVBF in newborn rats with an experimental model of stress-induced IH and adrenaline injection. Our analysis is based on the Doppler optical coherence tomography (DOCT) and a proposed adaptive wavelet-based approach that provides sensitive markers of abnormal reactions of the sagittal vein to external factors. The obtained results demonstrate that the incidence of IH in newborn rats is accompanied by a suppression of CVBF with the development of venous insufficiency and areactivity to adrenaline. We introduce a numerical measure θ, quantifying reactions of CVBF and show that the values θ < 1.23 estimated in the low-frequency (LF) spectral range corresponding to the sympathicus indicate abnormal reactions associated with the development of IH. We conclude that the revealed areactivity of the cerebral veins to adrenaline represents a possible mechanism responsible for pathological changes in CVBF